Body

Since its approval in April 2019, dacomitinib has been available for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations. The German Institute for Quality and Efficiency in Health Care (IQWiG) now examined in an early benefit assessment whether this drug offers an added benefit for patients in comparison with the appropriate comparator therapy. The result: While overall survival is longer under dacomitinib treatment, side effects, including severe events, are more frequent. Also, the patients' symptoms worsen earlier and more often than under the comparator treatment, and their health-related quality of life is worse. Overall, an added benefit in comparison with the appropriate comparator therapy is therefore not proven.

Only data on one of two research questions

The Federal Joint Committee (G-BA) distinguished between two research questions based on the mutation status in the EGFR gene of the tumour cells, since the effectiveness of the treatment options depends on the exact structure of this receptor. For the EGFR mutations "L858R" or "Del19", the appropriate comparator therapy was another drug of the same substance class, i.e. afatinib, gefitinib or erlotinib. Patients with other activating mutations were to be treated individually depending on the type of mutation in the comparator arm.

The drug manufacturer did not present study data on this second research question in its dossier, so that an added benefit of dacomitinib is not proven for this reason alone. For the first research question, there are data from the unblinded randomized controlled trial ARCHER 1050, in which patients - predominantly Asians - were treated with either dacomitinib or gefitinib.

Patients reported numerous disadvantages

With about 34 months, the median survival time in the dacomitinib arm of the study was just over seven months longer than in the gefitinib arm (just under 27 months). In addition, there were isolated advantages regarding certain side effects. However, this was offset by a large number of disadvantages: Numerous side effects, particularly including severe side effects, were more common under dacomitinib. Patient-reported symptoms worsened more frequently and also earlier. Deterioration of health-related quality of life was also more pronounced than under gefitinib.

"Particularly the deterioration in quality of life is remarkable; data are rarely as clear as they are here," says Thomas Kaiser, Head of IQWiG's Drug Assessment Department. "The patients found their global health status, their role functioning, their cognitive functioning and their social functioning to be more impaired than under gefitinib." Overall, the negative effects outweigh the positive effect on overall survival. An added benefit of dacomitinib in comparison with the appropriate comparator therapy is therefore not proven.

G-BA decides on the extent of added benefit

The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the G-BA. After publication of the dossier assessment, the G-BA conducts a commenting procedure and makes a final decision on the extent of the added benefit.

More English-language information will be available soon (Sections 2.1 to 2.5 of the dossier assessment as well as easily understandable information on informedhealth.org). If you would like to be informed when these documents are available, please send an e-mail to info@iqwig.de.

What The Study Did: A Montreal hospital moved from an older facility with ward-type rooms to a new facility with all private rooms and this analysis examined whether that was associated with reductions in multidrug-resistant organism colonization and health care-associated infections.

Authors: Todd C. Lee, M.D., M.P.H., of McGill University in Montreal, is the corresponding author.

(doi:10.1001/jamainternmed.2019.2798)

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

New research by Sussex scientists could be the first step towards developing a blood test to diagnose the most aggressive type of brain tumour, known as Glioblastoma.

A team from Professor Georgios Giamas' lab at the University of Sussex has identified novel biomarkers within bodily fluids, which signal the presence of the tumour.

Cancer biomarkers are molecules that are either exclusively found or over-expressed in cancer cells, as compared to 'normal', healthy cells. Biomarkers can be considered as biological signatures for a disease, as they indicate the presence of cancer in the body.

In a new paper published today in the Nature journal Communications Biology, Professor Georgios Giamas and his team describe particular biomarkers that are associated with extracellular vesicles - small 'packages' released by cells into bodily fluids so cells can communicate with each other.

The discovery suggests that bodily fluids like blood could be a simpler way to test for glioblastoma, rather than a biopsy, which is both invasive and painful for the patient as well as taking considerable time to get the results.

Georgios Giamas, Professor of Cancer Cell Signalling in the School of Life Sciences said: "At the moment, the outlook for glioblastoma patients is bleak. As the most aggressive type of brain tumour, survival rate is low.

"Our research provides more information about the markers which can signal the presence of glioblastoma - and the fact we've been able to identify ones that are associated with extracellular vesicles, suggests that there could be a way to use bodily fluids to test for the tumour in future."

Currently, a growing body of research is looking into the possibility of developing liquid-biopsies like blood tests to spot other types of cancers (e.g. pancreatic). Rather than taking a piece of tissue from a respective organ, liquid biopsies would allow doctors to take a small sample of blood and test for a range of biomarkers which will help identify the subtype of tumour.

Dr Thomas Simon, co-author of this study, highlighted that: "Liquid biopsies mean a less invasive procedure for patients, and arguably quicker results - something which is invaluable for those with an aggressive tumour that severely cuts life expectancy.

"But it could also mean better patient follow-up care, as a simple test can be carried out to check for the efficacy of existing treatments or for monitoring relapse.

"The more we know about biomarkers the better, so this is a step which should provide hope for anyone whose lives have been impacted by glioblastoma."

There are three sub-types of glioblastoma which all have biomarkers containing different information. The more researchers find out about these signatures, the more work can be done to improve the accuracy of diagnosis and to personalise treatment depending on the sub-type of cancer.

Rosemary Lane, a PhD student in Professor Giamas' lab and co-author of the study, added: "Glioblastoma subtyping is crucial for patient prognosis and personalised therapies. The fact that we can identify these molecular differences in extracellular vesicles is very exciting and will be of huge importance for discovering new biomarkers in the future."

Marian Vintu, a neurosurgeon and co-author, said: "Clinical research in brain cancer is such a powerful tool to expand our knowledge in this terrible disease and improve our patient's outcome."

The next step for Professor Giamas' team will be to test and validate the presence of these newly described biomarkers in glioblastoma patients.

The research, funded by the charity Action Against Cancer, suggests that this technique could ultimately become an option for diagnosing glioblastoma.

New research shows that brief parent-targeted interventions in the primary care setting can increase communication between parents and their teens about sexual and alcohol-related behavior. This method may serve as an important strategy for parents to influence adolescent behaviors and health outcomes.

Researchers from Children's Hospital of Philadelphia published the study today in JAMA Network Open.

"Community, school and home-based interventions involving direct contact between staff and parents or caregivers can favorably influence parent-teen communication and a wide range of adolescent risk-associated behaviors," said Carol A. Ford, MD, an adolescent medicine physician at Children's Hospital of Philadelphia and lead author of the study. "The purpose of this study was to see if these interventions could be shaped to also work out of a busy pediatric clinic."

This randomized, controlled trial, conducted between January 2016 and April 2018 in a busy primary care pediatric practice, involved 118 parents and caregivers and their 14- to 15-year-old adolescents. Almost all of the parents were female. Adolescent participants were evenly split by gender and age. Race and ethnicity of the adolescents reflected the practice's demographics: 53 percent black, 39 percent white and 94 percent non-Hispanic. At the start of the study, 13 percent of the adolescents reported a history of sex and 14 percent reported a history of drinking alcohol.

The parent-teen pairings were divided into three groups: sexual health intervention, alcohol intervention and a control group. During wellness visits, parents in the sexual health and alcohol intervention groups received coaching to discuss written materials encouraging parent-teen communication about sex or alcohol use, and their doctor endorsed these messages. Two weeks later, a health coach followed up with a phone call. The control group received standard medical care.

When the researchers followed up with the participants four months later, adolescents in both the sex intervention group and alcohol group reported more parent-teen communication about sex and alcohol than those in the control group. Parent-reported frequency of the parent-teen communication about sex or alcohol did not differ by group.

"Our study was not sufficiently long enough or large enough to test influences of parent-teen communication on adolescent behaviors," Ford said. "However, we adapted and tested interventions to show improvements in both parent-teen communication and associated risk-taking behaviors." This suggests doctors and nurses may have an important role in guiding parents and teens to discuss sensitive health topics, like sexual health and alcohol use, in a way that helps teens make healthy choices as they grow up."

Researchers from Osaka University, in cooperation with the Institute for Clinical Research and medical institutes participating in the Kansai Molecular Diagnosis Network for CNS Tumors (KNBTG), conducted the largest-ever retrospective cohort study for Japanese patients with glioblastoma (GBM), proposing an underlying prognosis biomarker responsible for the survival difference between two cohorts: an original Japanese cohort and a dataset from The Cancer Genome Atlas (TCGA). Their research results were published in Acta Neuropathologica Communications.

Clinical outcome of GBM has been reported to vary by region, and patients from Asia in particular have a better prognosis than those from any other region independent of treatment and social background. However, the cause of interregional survival differences in GBM remains poorly understood.

To unveil regional survival differences, the research team conducted genetic analysis of Japanese patients with the primary IDH-wildtype GBM registered in KNBTG. They investigated 140 KNBTG cases and 152 TCGA cases, both of which had been treated by current standard therapy (surgery followed by chemoradiation therapy), to conduct exploration of prognostic biomarkers and survival analysis.

As a result, there were molecular disproportions between these two cohorts, that is, there was unequal distribution of specific copy number alterations (CNAs), such as EGFR gain, CDKN2A deletion, and PTEN deletion. They found that the triple overlap CNAs in these loci (triple CNA) were much higher in frequency in TCGA (70.5%) than KNBTG (24.3%). In addition, triple CNA proved to be a common poor prognostic factor between KNBTG and TCGA. In patients who received standard treatment, median overall survival was 19.3 months for the KNBTG cohort and 15.6 months for the TCGA cohort, and this survival difference was highly associated with differences in the triple CNA frequency.

From these results, they found that triple CNA can be used as a prognosis biomarker and that the discrepancies in the distribution of triple CNA in these two cohorts could provide a full account of the cohort disparities of survival duration.

Toru Umehara from Osaka University said, "Besides GBM, several cancers in which the disproportion of the genetic landscape potentially varies the morbidity and clinical outcome have been reported. Even if the clinical outcome and genetic landscape of a disease are available from previous studies, it's important to create their own report and build an original database by region. Our research results will provide new insight into the interpretation and comparison of interregional clinical trials for GBM."

The liver plays a vital role as a filter in the human body. But what happens when it malfunctions? Researchers from the Universities of Geneva (UNIGE) and Lausanne (UNIL), the Vaud University Hospital Centre (CHUV), the Centre for Biomedical Imaging (CIBM), the Federal Polytechnic School of Lausanne (EPFL) and the University Hospitals of Geneva (HUG), Switzerland, teamed up to perform a detailed analysis of hepatic encephalopathy, a type of brain damage caused by chronic liver disease. The scientists were able to observe for the first time in a mouse model that a dysfunction of the liver provokes cerebral molecular disturbances in two weeks, even though no physical symptoms are apparent. Moreover, several molecules are concerned, including two that were previously unknown. The research results, which you can read about in the Journal of Hepatology, might help detect brain damage linked to liver diseases via a brain analysis before an individual's state of health deteriorates.

When the liver is diseased, as is the case with cirrhosis, a number of substances are no longer filtered, which can cause psychological, motor and neurocognitive disorders in adults. This disease, called hepatic encephalopathy, may manifest itself in a wide spectrum of symptoms, even including a coma. It is known that one of the actors in hepatic encephalopathy is ammonium. As Valérie McLin, professor in the Department of Paediatrics, Gynaecology and Obstetrics at UNIGE's Faculty of Medicine and Geneva University Hospitals (HUG), explains: "Ammonium is a substance produced when proteins break down, some of which is directed to the brain where it is transformed into glutamine - used for the production of neurotransmitters - while the other part is filtered by the liver and excreted in the urine." However, if the liver malfunctions, it causes an excess amount of ammonium in the brain, and therefore glutamine production, which can trigger cerebral edema and, in some cases, hepatic encephalopathy. There are still two unknown factors: are there other molecular actors responsible for hepatic encephalopathy? How long does it take for the brain to be affected by liver malfunction ?

Impact much earlier than anticipated

In an attempt to answer these questions, the researchers observed rats with chronic liver disease for eight weeks. "We tracked each animal individually by putting it in a high magnetic field MRI (9.4 Tesla) every two weeks so we could carry out high resolution spectroscopy (MRS). This meant we could observe the molecular alterations very precisely from the onset of the liver disease," says Dr Cristina Cudalbu, a research staff scientist and operational manager of the 9.4T MRI, Center for Biomedical Imaging at EPFL. "And we discovered hitherto unseen observations!"

The scientists found that molecular changes affect the brain as early as the second week of liver disease. And yet, the rats have minimal symptoms of the disease. "Based on earlier studies, we thought it will take about six weeks to see an impact, i.e. at the beginning of the deterioration of the animal's health," says Dr Cudalbu.

The external signs of the disease appear between the fourth and eighth week: jaundice, malnutrition or water in the belly. "From that moment, we observed that in addition to there being an excess of ammonium in the brain, the concentration of the two other molecules drops: vitamin C, an antioxidant, and creatine, which fulfils many functions, including energy-related functions," says Olivier Braissant, a professor in the Clinical Chemistry Department at CHUV and the Faculty of Biology and Medicine at the University of Lausanne (UNIL). This is the first time that the role these two new actors play in the disease has been visibly demonstrated. "These appear in a second phase after the ammonium in the blood rises," says Professor Braissant.

Should the brain be analysed to detect liver diseases?

The results suggest that an MRS brain scan might detect the neurological manifestations of chronic liver disease long before the appearance of the first symptoms. But the researchers also aim to know whether it would be possible to protect the brain from this type of deterioration - or at least reduce the damage - by compensating for the lack of creatine and vitamin C using supplements or through the use of probiotics. "We are also carrying out similar observations in humans to see whether the brain damage is similar to that in rats," concludes Professor McLin.

A new study from Washington University School of Medicine in St. Louis supports evidence that children with mild asthma can effectively manage the condition by using their two inhalers -- one a steroid and the other a bronchodilator -- when symptoms occur. This is in contrast to the traditional method of using the steroid daily, regardless of symptoms, and the bronchodilator when symptoms occur. The as-needed use of both inhalers is just as effective for mild asthma as the traditional protocol, according to the investigators.

The steroid inhaler lowers inflammation, and the bronchodilator -- also known as a rescue inhaler -- relaxes the airway during an asthma attack to quickly make breathing easier.

The research focused on African American children, who are disproportionately affected by asthma. The study appears in the Journal of Allergy and Clinical Immunology: In Practice.

"We were pleased to find that as-needed treatment based on symptoms can deliver similar asthma control with less medication," said first author Kaharu Sumino, MD, an associate professor of medicine. "Patients in the group that used both inhalers as needed used about one-fourth the steroid dose of the group that inhaled a prescribed daily amount. We also were pleased to see that the patients and families felt that they had more ownership over their asthma management when practicing as-needed treatment."

In the U.S., about 6.2 million children under age 18 have asthma. Among white children, about 7.4 percent have asthma. Among African American children, that statistic is almost double, at 13.4 percent. According to the Allergy and Asthma Foundation of America, asthma attacks account for 1.8 million emergency room visits per year, and African Americans are three times more likely than average to be hospitalized due to asthma.

The study was conducted by primary care doctors at multiple pediatric practices throughout the St. Louis area, suggesting the strategy is widely applicable in a primary care setting and not just effective when implemented by researchers at a single academic medical center.

Past clinical trials conducted in the highly controlled settings of academic medical centers had suggested that the medication-as-needed approach worked just as well as a traditional strategy of daily scheduled steroid treatments with a rescue inhaler as needed. But how well that strategy might transfer to individual community medical practices had been an open question. Not only is this alternative, as-needed, symptom-based strategy effective when administered by the children's primary care doctors, the researchers found that approach reduced the amount of steroid medication the children took monthly by almost 75 percent.

The study included 206 African American children 6 to 17 years of age with mild asthma that was adequately controlled with asthma controller steroid medication. Participants saw their own pediatricians at 12 primary care providers throughout St. Louis. The patients were randomly assigned to one of two groups. Each participant in one group was advised to take a dose from an inhaler containing the steroid beclomethasone as needed when symptoms arose, along with the rescue bronchodilator albuterol. Symptoms that might prompt the use of medication include shortness of breath, tightness in the chest, coughing, wheezing and difficulty performing physical activities.

Each participant in the second group was advised to take a specific inhaled dose of the steroid beclomethasone daily, regardless of symptoms, plus the rescue bronchodilator as needed in response to symptoms, as has been the standard recommendation for almost 30 years by the Global Initiative for Asthma guidelines.

At the end of the one-year study, the researchers found no differences between groups in surveys of how well the patients' asthma was controlled, as well as no differences in breathing tests that measure lung function. There also were no differences in the number of participants who sought extra medical care -- such as office or emergency room visits -- for asthma attacks.

As might be expected, the group taking daily beclomethasone, an inhaled corticosteroid, used more of the medication per month than those in the symptom-based group. On average, children in the daily-use group used 1,961 micrograms per month, while the symptom-based group used 526 micrograms per month, cutting the amount of this medication by almost three-fourths. The reduced amount is desirable, according to the investigators, because steroids have side effects that include stunted growth.

"Many families are concerned about the cost of this medication as well as the growth-related side effects, and stop taking their steroid medicine altogether. So it's nice to show that less medication -- used as needed -- is just as effective," Sumino said. "This as-needed steroid plus rescue albuterol strategy is now recommended in the Global Initiative for Asthma guidelines as one of the options for the treatment of mild asthma. Given the result of our study and others, primary care doctors may tell their patients with mild asthma that they have an alternative effective strategy other than taking the inhaled steroid every day, if they prefer not to do so."

The researchers also noted that children and caregivers in the group taking medication as needed reported that they felt they were actively managing their asthma care rather than passively relying on doctors' orders. The symptom-based strategy, in other words, gave them a sense of ownership over their asthma management, which is important in the long-term control of the disease, according to the Sumino and her colleagues.

When a child suffers a head trauma, medical professionals are in high gear to prevent further damage to a developing brain. Measuring and regulating the child's level of carbon dioxide is critical to ensuring the brain is getting enough blood oxygen to prevent a secondary brain injury. High carbon dioxide can increase intracranial pressure, while a low level is associated with poor brain circulation.

The Harborview Injury Prevention and Research Center (HIPRC) developed a protocol for a standardized response to these events. The guidelines, released earlier this year, are used at Harborview Medical Center, the region's Level I pediatric trauma center where about 120 pediatric brain-trauma patients receive care each year.

But there are no guidelines on whether a noninvasive method of measuring carbon dioxide from patients' exhalations, known as end-tidal capnography, is as effective as drawing blood through a child's artery.

In a study published Aug. 16 in JAMA Network Open, HIPRC researchers answered that clinical question: Measuring the carbon dioxide level through an artery is still the most accurate diagnostic for pediatric brain trauma.

"To maintain appropriate carbon dioxide levels, we still need to use the gold-standard approach," said Dr. Jen-Ting Yang, a fellow physician in anesthesiology and pain medicine at the University of Washington School of Medicine.

Sampling carbon dioxide through the artery is considered the gold standard, but end-tidal carbon dioxide is widely used in clinical practice because placing an arterial line in a child is challenging and complications are not uncommon.

In a study of the two ways to detect carbon dioxide, Yang and colleagues found low agreement between using an arterial line and end-tidal capnography. The researchers analyzed the cases of 137 children under age 18 who were admitted to Harborview's Pediatric Intensive Care Unit between 2011 and 2017. Among these children, researchers had 445 paired data points from both diagnostic methods.

Overall, just 42 percent of paired data agreed (187 data points out of 445). The agreement was even lower during the first eight hours after admission, and with development of pediatric acute respiratory distress syndrome.

Monica Vavilala, HIPRC director and a UW professor of anesthesiology and pain medicine, said given how commonly clinicians use end-tidal derived carbon dioxide levels to adjust ventilation parameters, researchers were hoping that end-tidal capnography would be just as effective. But, she said, she is glad they were able to identify the preferred method.

"We've been able to use the evidence from patients with brain trauma to provide a better roadmap for what is agreed-upon as good quality care," she said.

Patients who meet an addiction medicine consult team while they're in the hospital are twice as likely to participate in treatment for substance use disorder after they go home, according to new research.

The study, published today in the Journal of General Internal Medicine, measured one key outcome for patients who participated in a first-of-its-kind addiction intervention program started by Oregon Health & Science University in 2015.

"This confirms that hospitalization is a reachable moment," said lead author Honora Englander, M.D., an associate professor of medicine in the OHSU School of Medicine. "We were able to sizably increase treatment engagement. That matters because treatment is associated with reduced health care costs, reduced mortality and a whole vast array of really important outcomes."

Project IMPACT, or Improving Addiction Care Team, brings together physicians, social workers, peer-recovery mentors and community addiction providers to address addiction when patients are admitted to the hospital. Englander is the project director.

The new study compared 208 patients who received addiction medicine consultation at OHSU with a control group of Medicaid patients with similar conditions hospitalized in any Oregon hospital. The study compared the substance use treatment engagement in the month after they were released from the hospital.

A total of 38.9% of IMPACT patients engaged in substance use treatment, compared with 23.3% of similar patients who did not work with IMPACT.

Most hospitals do not treat substance use disorder during hospitalization or connect people to treatment after discharge, and hospitalizations related to addiction are extremely costly. Hospitals may lack the staffing, financial resources, or interest in taking on addiction care.

However, people with substance use disorder often end up hospitalized, sometimes as a result of illness arising from their addiction. Examples include endocarditis caused by injection drug use, liver disease from overuse of alcohol, or various kinds of trauma.

Hospitals are well-equipped to handle the acute medical need, but not the underlying addiction.

"Stigma is a huge driver," Englander said. "People don't think of addiction as something that hospitals should be addressing. Our study pushes back at that."

OHSU's program is one of only a handful in the nation, which remains beset by an opioid epidemic and a rising methamphetamine crisis that claimed more than 70,000 lives in 2017. The new study indicates the program makes a difference in engaging people in treatment.

"Hospital-based addiction medicine care can improve (substance use disorder) treatment engagement, which is associated with reduced substance use, mortality, and other important clinical outcomes," the authors write. "National expansion of such models represents an opportunity to address an enduring gap in the SUD treatment continuum."

Studying mutant worms has led to the discovery of a receptor that reduces sensitivity to opioid side effects in these organisms. The work implicates the understudied GPR139 receptor in the toxic effect of these painkillers; the authors say GPR139 could be a useful target for increasing opioid safety. Despite side effects like addiction and dependency, opioids such as morphine and fentanyl remain the standard of care for pain relief. These drugs target the mu opioid peptide receptor (MOR). A better understanding of the MOR receptor system is needed to avoid problems with side effects and addiction, though identifying molecular mechanisms that regulate opioid MOR receptor activity has been challenging. Here, researchers led by Dandan Wang developed a platform that would allow for the genetic discovery of proteins that modified MOR signaling. As part of their work, they engineered mutations in about 2,500 Caenorhabditis elegans nematodes. By studying these and also control nematodes, they identified hundreds of organisms with increased sensitivity to opioids. In experiments attempting to reduce this sensitivity, the researchers uncovered a regulator of mu opioid peptide receptor signaling, GPR139, that made the worms less sensitive to opioid side effects. In further studies in mice, deletion of GPR139 enhanced morphine’s analgesic effect but reduced withdrawal effects. “Our results suggest that GPR139 could potentially be exploited pharmacologically for increasing safety and efficacy of opioid pharmacotherapy,” the authors say.

In the current issue of Cardiovascular Innovations and Applications volume 4, issue 2, pp. 125-134; DOI https://doi.org/10.15212/CVIA.2019.0013, Xiaoyu Zheng, Qingyao Liao, Yue Wang, Hua Li, Xiaodong Wang, Yaohui Wang, Wentao Wu, Junlin Wang, Ling Xiao, and Jing Huang. from the Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China and the Institute of Acoustics, Chinese Academy of Sciences, Beijing, China summarize the biomedical effects of acoustic intervention in experimental and clinical studies, current challenges, and the potential of ultrasound for cardiovascular disease therapy.

Ultrasound can be considered a mechanical wave for both clinical diagnostic and therapeutic purposes on the basis of its good penetrability and directivity while spreading in solid organs or tissues without any ionizing radiation. As a powerful form of energy, ultrasound, is used for deep-tissue therapy with different sonication parameters. The feasibility of minimally invasive or noninvasive acoustic treatment of a variety of diseases, such as hypertension, arrhythmia, hypertrophic cardiomyopathy, and myocardial infraction, is being explored in animal experiments and clinical trials. In this review, we summarize the biomedical effects of acoustic intervention in experimental and clinical studies, current challenges, and the potential of ultrasound for cardiovascular disease therapy.

In the current issue of Cardiovascular Innovations and Applications volume 4, issue 2, pp. 135-141; DOI https://doi.org/10.15212/CVIA.2019.0015, Ömer Şatıroğlu, Murtaza Emre Durakoğlugil, Hüseyin Avni Uydu, Hakan Duman, Mustafa Çetin, Yüksel Çiçek, and Turan Erdoğan. from the Department of Cardiology, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey and the Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey consider the relationship between mean platelet volume and in-hospital mortality in geriatric patients with ST segment elevation myocardial infarction who underwent primary percutaneous coronary intervention.

In this study, patients in the high-MPV group were older, more of them had three-vessel disease, and they had higher in-hospital mortality. Patients with in-hospital death were older, had higher Gensini score, creatinine concentration, and MPV, and had lower HDL cholesterol concentration. MPV, age, HDL cholesterol concentration, creatinine concentration, and Gensini score were found to be independent predictors of in-hospital death. These results suggest that high admission MPV levels are associated with increased in-hospital mortality in geriatric patients with STEMI undergoing primary PCI.

Women with severe sleep apnea appear to be at an elevated risk of getting cancer, a study shows. No causal relationship is demonstrated, but the link between nocturnal hypoxia in women and higher cancer risk is still clear.

"It's reasonable to assume that sleep apnea is a risk factor for cancer, or that both conditions have common risk factors, such as overweight. On the other hand, it is less likely that cancer leads to sleep apnea," notes Ludger Grote, Adjunct Professor and chief physician in sleep medicine, and the last author of the current study.

The research, published in the European Respiratory Journal, is based on analyses of registry data, collected in the European database ESADA, on a total of some 20,000 adult patients with obstructive sleep apnea (OSA). About 2 percent of them also had a cancer diagnosis.

As expected, advanced age was associated with elevated cancer risk, but adjusting the data for age, gender, body mass index (BMI), smoking, and alcohol consumption nevertheless showed a possible link between intermittent hypoxia at night and higher cancer prevalence. The connection applied mainly to women, and was weaker in men.

"Our results indicate a cancer risk that's elevated two- to three-fold among women with pronounced sleep apnea. It's impossible to say for sure what causes underlie the association between sleep apnea and cancer, but the indication means we need to study it in more depth," Grote says.

Ludger Grote is Adjunct Professor of Pulmonary Medicine, specializing in sleep medicine, at Sahlgrenska Academy, University of Gothenburg. He is also a senior consultant and head of medicine at the Department of Sleep Medicine at Sahlgrenska University Hospital.

"The condition of sleep apnea is well known to the general public and associated with snoring, daytime fatigue, and elevated risk of cardiovascular disease, especially in men. Our research paves the way for a new view -- that sleep apnea may possibly be connected with increased cancer risk, especially in women," Grote says.

Previous studies have shown that, more often than others, people with sleep apnea have a cancer diagnosis in their medical history. Research in this area is expanding, while the gender aspects have hardly been explored.

"Above all, the focus has been on the connection with one form of cancer: malignant melanoma. Cancer of the breast or womb may now become a new area. There may be a combined effect of female sex hormones and stress activation, induced by nocturnal hypoxia in sleep apnea, that can trigger cancer development or a weakening of the body's immune system."

The first large-scale review into the health outcomes of people living with HIV has found that this group has an increased risk of contracting specific diseases and illnesses, some of which are more commonly associated with ageing.

The umbrella review, led by academics from Anglia Ruskin University (ARU) in Cambridge and the Medical University of Vienna, combined data from 20 separate observational studies and examined 55 different illnesses.

Published this week in the journal Clinical Infectious Diseases, the study found that people living with HIV have a significantly elevated risk of Chronic Obstructive Pulmonary Disease (COPD) and coughs, heart disease, pregnancy mortality and sepsis, anemia, and bone fractures.

Although the number of people contracting HIV is declining, approximately 1.8 million people are infected every year and HIV remains one of the world's major health issues.

In recent years, people living with HIV have benefited from improved access to antiretroviral treatment. However, increased life expectancy and a lower immunity has meant higher levels of comorbidity, with people living with HIV also more likely to suffer from other illnesses.

The greater prevalence of age-associated diseases may be explained by the persistent immunodeficiency and inflammation connected with HIV. There are also adverse effects associated with antiretroviral treatment.

Previous studies have also suggested that people living with HIV in developed countries, as a population, often exhibit greater risk factors associated with non-AIDS related illnesses, such as smoking, drug use and alcohol use.

Senior author Dr Lee Smith, Reader in Physical Activity and Public Health at Anglia Ruskin University (ARU), said: "There has been a major shift in how we view HIV. It is no longer a death sentence but rather a manageable chronic illness.

"By pooling data from different studies, we've been able to show for the first time that even with the rise in life expectancy amongst people living with HIV, this population now seems to be disproportionately affected by chronic illnesses often attributable to lifestyle issues such as smoking, drug and alcohol use, or more commonly associated with an older population.

"We're unable to say for certain which are caused or exacerbated by HIV and its treatment, and which are related to lifestyle. However, the elevated risk levels highlighted in our study should hopefully lead to further research to improve both the prevention and early detection of these comorbidities in people living with HIV. Public health bodies worldwide should reflect on these findings."

BOSTON - Pancreatic cancer is one of the deadliest cancers with limited treatment options. It typically comes with an especially poor prognosis due to its lack of symptoms until advanced stages and its ability to resist many anticancer therapies. Identifying genes involved in its development may lead to earlier diagnoses and improved treatments.

Now a research team led by investigators at Massachusetts General Hospital (MGH), Brigham and Women's Hospital, and Dana-Farber Cancer Institute has found that mutations in a particular gene are associated with hereditary forms of pancreatic cancer. The group also uncovered a mechanism by which these mutations may contribute to the development of tumors.

In their study, which is published in Nature Genetics, the researchers sequenced the genomes of a family in which multiple members had pancreatic cancer. The analyses revealed a mutation in the member of the RAS oncogene family-like 3 (RABL3) gene.

To assess the effects of this gene mutation, the investigators recapitulated it in zebrafish, a model which offers large populations for studying the impact of newly discovered genetic mutations on cancer risk. The fish carrying the mutation developed cancers at an accelerated rate and with greater frequency.

Additional studies revealed that the protein expressed by RABL3 interacts with components of the RAS signaling pathway, which has been implicated in various forms of cancer and other conditions. Because aberrant RAS pathway signaling is found in most pancreatic cancers, research into how RABL3 impacts the RAS pathway could offer new strategies for targeted therapy.

"This work is a prime example for 'bedside-to-fish tank and back,' where we start with a patient story and their family history, and use genetic methods to identify a gene mutation that we then confirm in the zebrafish model to ultimately discover novel diagnostic tests and targets for potential therapy," said senior author Wolfram Goessling, MD, PhD, Chief of the Division of Gastroenterology at MGH.

The findings may also provide an explanation for other families with multiple cases of pancreatic cancer, noted lead author Sahar Nissim, MD, PhD, a cancer geneticist and gastroenterologist at the Dana-Farber Cancer Institute and Brigham and Women's Hospital. "More broadly, this work highlights the power of studying and understanding rare family syndromes: from just one family, we may gain precious clues to why pancreatic cancer happens, how we may prevent it or catch it earlier, and how we may treat it more effectively," Nissim said.

Testing for this genetic mutation, especially in individuals with a strong family history of pancreatic cancer, may be warranted in the future. Also, additional studies may reveal insights on how well patients respond to different treatments based on whether their pancreatic cancer is associated with this or other inherited genetic mutations.