Klop B.,Center for Diabetes and Vascular Medicine |
Rego A.T.D.,Institute for Health Research |
Cabezas M.C.,Center for Diabetes and Vascular Medicine
Current Opinion in Lipidology | Year: 2013
Purpose of review: This study reviews recent developments concerning the effects of alcohol on plasma triglycerides. The focus will be on population, intervention and metabolic studies with respect to alcohol and plasma triglycerides. Recent findings: Alcohol consumption and fat ingestion are closely associated and stimulated by each other via hypothalamic signals and by an elevated cephalic response. A J-shaped relationship between alcohol intake and plasma triglycerides has been described. A normal body weight, polyphenols in red wine and specific polymorphisms of the apolipoprotein A-V and apolipoprotein C-III genes may protect against alcohol-associated hypertriglyceridemia. In contrast, obesity exaggerates alcohol-associated hypertriglyceridemia and therefore the risk of pancreatitis. Summary: High alcohol intake remains harmful since it is associated with elevated plasma triglycerides, but also with cardiovascular disease, alcoholic fatty liver disease and the development of pancreatitis. Alcohol-induced hypertriglyceridemia is due to increased very-low-density lipoprotein secretion, impaired lipolysis and increased free fatty acid fluxes from adipose tissue to the liver. However, light to moderate alcohol consumption may be associated with decreased plasma triglycerides, probably determined by the type of alcoholic beverage consumed, genetic polymorphisms and lifestyle factors. Nevertheless, patients should be advised to reduce or stop alcohol consumption in case of hypertriglyceridemia. © 2013 Wolters Kluwer Health.
News Article | September 13, 2016
Thirty-one new gene regions linked with blood pressure have been identified in one of the largest genetic studies of blood pressure to date, involving over 347,000 people, and jointly led by Queen Mary University of London (QMUL) and the University of Cambridge. The discoveries include DNA changes in three genes that have much larger effects on blood pressure in the population than previously seen, providing new insights into the physiology of hypertension and suggesting new targets for treatment. High blood pressure or hypertension is a major risk factor for cardiovascular disease and premature death. It is estimated to be responsible for a larger proportion of global disease burden and premature mortality than any other disease risk factor. However, there is limited knowledge on the genetics of blood pressure. The teams investigated the genotypes of around 347,000 people and their health records to find links between their genetic make-up and cardiovascular health. The participants included healthy individuals and those with diabetes, coronary artery disease and hypertension, from across Europe, (including the UK, Denmark, Sweden, Norway, Finland and Estonia), the USA, Pakistan and Bangladesh. The study brought together around 200 investigators from across 15 countries. Study author Professor Patricia Munroe from QMUL said: "We already know from earlier studies that high blood pressure is a major risk factor for cardiovascular disease. Finding more genetic regions associated with the condition allows us to map and understand new biological pathways through which the disease develops, and also highlight potential new therapeutic targets. This could even reveal drugs that are already out there but may now potentially be used to treat hypertension." Most genetic blood pressure discoveries until now have been of common genetic variants that have small effects on blood pressure. The study, published in Nature Genetics, has found variants in three genes that appear to be rare in the population, but have up to twice the effect on blood pressure. Study author, Dr Joanna Howson from the University of Cambridge said: "The sheer scale of our study has enabled us to identify genetic variants carried by less than one in a hundred people that affect blood pressure regulation. While we have known for a long time that blood pressure is a risk factor for coronary heart disease and stroke, our study has shown that there are common genetic risk factors underlying these conditions." RBM47 is a gene that encodes for a protein responsible for modifying RNA. RRAS is involved in cell cycle processes and has already been implicated in a syndrome related to 'Noonan syndrome' which is characterised by heart abnormalities. COL21A1 is involved in collagen formation in many tissues, including the heart and aorta. COL21A1 and RRAS warrant particular interest since both are involved in blood vessel remodelling, with relevance to hypertension. The team also found a mutation in a key molecule ENPEP that affects blood pressure. This gene codes for an enzyme that is a key molecule involved in regulating blood pressure through the dilation and constriction of blood vessels, and is currently a therapeutic target. Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation which part-funded the research, said: "Large scale genetic studies continue to expand the number of genes that may contribute to the development of heart disease, or risk factors such as high blood pressure. But so far most of the genes discovered in these studies individually have only very small effects on risk - though they may still provide valuable clues for new drug targets. "This study has increased the number of genes implicated in control of blood pressure to almost 100 and, in the process, has also identified three genes that have larger effects on blood pressure than previously found." The study was also funded by the National Institute for Health Research (NIHR), National Institute of Health (NIH), Wellcome Trust and the Medical Research Council. A complementary study in Nature Genetics, co-led by Patricia Munroe (QMUL) and Christopher Newton-Cheh (Harvard Medical School), finds 17 new gene regions involved in blood pressure regulation that play a role in tissues beyond the kidneys.
News Article | October 5, 2015
WALTHAM, Mass.--(BUSINESS WIRE)--Josh Bregman, Vice President at Conjur, Inc., provider of security orchestration software, is presenting, “Using Puppet with a Secret Server,” at PuppetConf 2015, taking place on Monday, October 5 – Friday, October 9, 2015 in Portland, Oregon. Sessions at PuppetConf range from how to get started with Puppet, modules and related technologies, to advanced tips and tricks for using Puppet, PuppetDB, Razor, Facter and more. Software by Puppet Labs, the leading provider of IT automation software, provides system administrators the operational agility, efficiency and insight they need to proactively manage dynamic infrastructure, scaling from tens of servers to thousands, both on premise and in the cloud. The year 2015 is shaping up as the “year of the secrets server,” with numerous open source and commercial options now available. Secrets servers offer important advantages compared to storing secrets in configuration management. From a security standpoint, secrets servers speed the path to security and compliance certification, offering capabilities such as end-to-end encryption, access control, detailed auditing of access, purpose-built APIs, dedicated management and reporting tools, and support for auto-scaling deployment architectures. Furthermore, using a secrets server enables DevOps teams to roll back the “lockdown” and re-establish the collaborative workflows that configuration management was developed to encourage. Josh Bregman has 20 years of experience successfully architecting, evangelizing and delivering innovative identity management and security products to customers. Prior to joining Conjur, Josh spent a decade as a solutions and pre-sales leader in the Oracle ecosystem. A developer at heart, early in his career Josh worked as a software engineer at IBM, GTE Labs and Netegrity. He has two U.S. patents and received a bachelor’s degree in math from the University of Rochester. Follow Josh on Twitter @kingoauth. Conjur is a Silver Sponsor of PuppetConf 2015. For more information, visit: https://2015.puppetconf.com. About Conjur, Inc. Conjur provides security orchestration software to manage, enforce and audit infrastructure applications with modern IT systems including Chef, Docker, Jenkins, Amazon Web Services, Open Stack, Cloud Foundry, Microsoft Azure and Puppet Labs. The company provides best practice reference architectures and standards based open source tools so that security best practices can become part of every software development activity and IT environment. Customers include Netflix, Genome Bridge, OpenDNS and Rally Software, among others. Founded in 2012, Conjur is based in Waltham, Massachusetts. Investors include Avalon Partners, Amplify Partners and Andy Palmer (Founder of Koa Labs). Visit: www.conjur.net and follow on Twitter @conjurinc.
Type 'depression' into the Apple App Store and a list of at least a hundred programs will pop up on the screen. There are apps that diagnose depression (Depression Test), track moods (Optimism) and help people to “think more positive” (Affirmations!). There's Depression Cure Hypnosis (“The #1 Depression Cure Hypnosis App in the App Store”), Gratitude Journal (“the easiest and most effective way to rewire your brain in just five minutes a day”), and dozens more. And that's just for depression. There are apps pitched at people struggling with anxiety, schizophrenia, post-traumatic stress disorder (PTSD), eating disorders and addiction. This burgeoning industry may meet an important need. Estimates suggest that about 29% of people will experience a mental disorder in their lifetime1. Data from the World Health Organization (WHO) show that many of those people — up to 55% in developed countries and 85% in developing ones — are not getting the treatment they need. Mobile health apps could help to fill the gap (see 'Mobilizing mental health'). Given the ubiquity of smartphones, apps might serve as a digital lifeline — particularly in rural and low-income regions — putting a portable therapist in every pocket. “We can now reach people that up until recently were completely unreachable to us,” says Dror Ben-Zeev, who directs the mHealth for Mental Health Program at the Dartmouth Psychiatric Research Center in Lebanon, New Hampshire. Public-health organizations have been buying into the concept. In its Mental Health Action Plan 2013–2020, the WHO recommended “the promotion of self-care, for instance, through the use of electronic and mobile health technologies.” And the UK National Health Service (NHS) website NHS Choices carries a short list of online mental-health resources, including a few apps, that it has formally endorsed. But the technology is moving a lot faster than the science. Although there is some evidence that empirically based, well-designed mental-health apps can improve outcomes for patients, the vast majority remain unstudied. They may or may not be effective, and some may even be harmful. Scientists and health officials are now beginning to investigate their potential benefits and pitfalls more thoroughly, but there is still a lot left to learn and little guidance for consumers. “If you type in 'depression', its hard to know if the apps that you get back are high quality, if they work, if they're even safe to use,” says John Torous, a psychiatrist at Harvard Medical School in Boston, Massachusetts, who chairs the American Psychiatric Association's Smartphone App Evaluation Task Force. “Right now it almost feels like the Wild West of health care.” Electronic interventions are not new to psychology; there is robust literature showing that Internet-based cognitive behavioural therapy (CBT), a therapeutic approach that aims to change problematic thoughts and behaviours, can be effective for treating conditions such as depression, anxiety and eating disorders. But many of these online therapeutic programmes are designed to be completed in lengthy sessions in front of a conventional computer screen. Smartphone apps, on the other hand, can be used on the go. “It's a way of people getting access to treatment that's flexible and fits in with their lifestyle and also deals with the issues around stigma — if people are not quite ready to maybe go and see their doctor, then it might be a first step to seeking help,” says Jen Martin, the programme manager at MindTech, a national centre funded by the United Kingdom's National Institute for Health Research and devoted to developing and testing new mental-health technologies. One of the best-known publicly available apps was devised to meet that desire for flexibility. In 2010, US government psychologists conducting focus groups with military veterans who had PTSD learned that they wanted a tool they could use whenever their symptoms flared up. “They wanted something that they could use in the moment when the distress was rising — so when they were in line at the supermarket,” says Eric Kuhn, a clinical psychologist and the mobile apps lead at the US Department of Veterans Affairs' National Center for PTSD. The department joined up with the US Department of Defense to create PTSD Coach, a free smartphone app released in early 2011. Anyone who has experienced trauma can use the app to learn more about PTSD, track symptoms and set up a support network of friends and family members. The app also provides strategies for coping with overwhelming emotions; it might suggest that users distract themselves by finding a funny video on YouTube or lead users through visualization exercises. In its first three years in app stores, PTSD Coach was downloaded more than 150,000 times in 86 different countries. It has shown promise in several small studies; in a 2014 study of 45 veterans, more than 80% reported that the app helped them to track and manage their symptoms and provided practical solutions to their problems2. More results are expected soon. Kuhn and his colleagues recently completed a 120-person randomized trial of the app, and a Dutch team is currently analysing data from a 1,300-patient trial on a similar app called SUPPORT Coach. Smartphone apps can also interact with users proactively, pinging them to ask about their moods, thoughts and overall well-being. Ben-Zeev created one called FOCUS, which is geared towards patients with schizophrenia. Several times a day, the app prompts users to answer questions such as “How well did you sleep last night?” or “How has your mood been today?” If users report that they slept poorly, or have been feeling anxious, the app will suggest strategies for tackling that problem, such as limiting caffeine intake or doing some deep-breathing exercises. Some apps help people to stay connected to health-care professionals, too. ClinTouch, a psychiatric-symptom-assessment app designed by researchers at the University of Manchester, UK, analyses users' responses for signs that they may be experiencing a relapse; it can even notify a clinical-care team. Small feasibility studies — which are generally designed to determine whether an intervention is practical, but do not necessarily evaluate its efficacy — have shown that patients use and like both apps, and a 2014 study found that those who used FOCUS for a month experienced a reduction in psychotic symptoms and depression3. FOCUS and ClinTouch are both now being evaluated in randomized, controlled trials. Some researchers see opportunities in the data that smartphones collect about their users' movement patterns or communication activity, which could provide a potential window into mental health. “Your smartphone is really this interesting diary of your life,” says Anmol Madan, the co-founder and chief executive of Ginger.io, a digital mental-health company based in San Francisco, California. Studies have now shown that certain patterns of smartphone use can predict changes in mental-health symptoms4; a drop in the frequency of outgoing text messages, for instance, may suggest that a user's depression is worsening. The Ginger.io app, which is still in beta, monitors these sorts of patterns and alerts each user's assigned mental-health coach if it detects a worrying change. The evidence supporting the use of such apps is building5, 6, 7. But this is a science in its infancy. Much of the research has been limited to pilot studies, and randomized trials tend to be small and unreplicated. Many studies have been conducted by the apps' own developers, rather than by independent researchers. Placebo-controlled trials are rare, raising the possibility that a 'digital placebo effect' may explain some of the positive outcomes that researchers have documented, says Torous. “We know that people have very strong relationships with their smartphones,” and receiving messages and advice through a familiar, personal device may be enough to make some people feel better, he explains. But the bare fact is that most apps haven't been tested at all. A 2013 review8 identified more than 1,500 depression-related apps in commercial app stores but just 32 published research papers on the subject. In another study published that year9, Australian researchers applied even more stringent criteria, searching the scientific literature for papers that assessed how commercially available apps affected mental-health symptoms or disorders. They found eight papers on five different apps. The same year, the NHS launched a library of “safe and trusted” health apps that included 14 devoted to treating depression or anxiety. But when two researchers took a close look at these apps last year, they found that only 4 of the 14 provided any evidence to support their claims10. Simon Leigh, a health economist at Lifecode Solutions in Liverpool, UK, who conducted the analysis, says he wasn't shocked by the finding because efficacy research is costly and may mean that app developers have less to spend on marketing their products. A separate analysis11 found that 35 of the mobile health apps originally listed by the NHS transmitted identifying information — such as e-mail addresses, names and birthdates — about users over the Internet, and two-thirds of these did not encrypt the data. Last year, the NHS took this apps library offline and posted a smaller collection of recommended online mental-health services. The NHS did not respond to e-mailed questions or make an official available for interview, but it did provide this statement: “We are working to upgrade the Health Apps Library, which was launched as a pilot site in 2013 to review and recommend apps against a defined set of criteria which included data protection.” The regulation of mental-health apps is opaque. Some apps designed to be used in a medical context can be considered medical devices and therefore may be regulated by the UK Medicines and Healthcare Products Regulatory Agency, the US Food and Drug Administration (FDA) or equivalent bodies elsewhere. But the lines are fuzzy. In general, an app that claims to prevent, diagnose or treat a specific disease is likely to be considered a medical device and to attract regulatory scrutiny, whereas one that promises to 'boost mood' or provide 'coaching' might not. The FDA has said that it will regulate only those health apps that present the highest risks to patients if they work improperly; even mental-health apps that qualify as medical devices might not be regulated if the agency deems them to be relatively low risk. But the potential risks are not well understood. “At the low end, people might waste their money or waste their time,” says Martin, “and at the higher end, especially with mental health, they might be actively harmful or giving dangerous advice or preventing people from going and getting proper treatment.” When a team of Australian researchers reviewed 82 commercially available smartphone apps for people with bipolar disorder12, they found that some presented information that was “critically wrong”. One, called iBipolar, advised people in the middle of a manic episode to drink hard liquor to help them to sleep, and another, called What is Biopolar Disorder, suggested that bipolar disorder could be contagious. Neither app seems to be available any more. Martin says that in Europe, at least, apps tend to come in two varieties, those that are commercially developed and come with little supporting evidence or plans for evaluation, and those with academic or government backing that take a more rigorous approach. The problem is that the former are generally more engaging for users and the latter take so long to make it to the market — if they even do — that they look out of date. “This is a generalization,” Martin says, “but it's broadly true.” Even well-intentioned apps can produce unpredictable outcomes. Take Promillekoll, a smartphone app created by Sweden's government-owned liquor retailer, designed to help curb risky drinking. While out at a pub or a party, users enter each drink they consume and the app spits out an approximate blood-alcohol concentration. When Swedish researchers tested the app on college students, they found that men who were randomly assigned to use the app ended up drinking more frequently than before, although their total alcohol consumption did not increase. “We can only speculate that app users may have felt more confident that they could rely on the app to reduce negative effects of drinking and therefore felt able to drink more often,” the researchers wrote in their 2014 paper13. It's also possible, the scientists say, that the app spurred male students to turn drinking into a game. “I think that these apps are kind of playthings,” says Anne Berman, a clinical psychologist at the Karolinska Institute in Stockholm and one of the study's authors. There are other risks too. In early trials of ClinTouch, researchers found that the symptom-monitoring app actually exacerbated symptoms for a small number of patients with psychotic disorders, says John Ainsworth at the University of Manchester, who helped to develop the app. “We need to very carefully manage the initial phases of somebody using this kind of technology and make sure they're well monitored,” he says. In a pilot trial published earlier this year, ten US veterans with PTSD were randomly assigned to use PTSD Coach on their own for eight weeks, while another ten used the app with the support and guidance of primary-care providers. At the end of the trial, seven of the ten patients using the app with support showed a reduction in PTSD symptoms, compared with just three of the patients who used the app on their own14. But if apps require medical supervision, that undermines the idea that they will serve as an easy and low-cost way to provide care to the masses. “People think there's an app for everything,” says Helen Christensen, the director of the Black Dog Institute at the University of New South Wales in Sydney, Australia, who has developed and studied mental-health apps. “It's actually about how we build systems around apps, so that people have health care.” Distributing mental-health apps in the developing world presents further challenges. Although mobile technology is spreading rapidly, there are many people who do not have — or cannot afford — smartphones or mobile Internet access. And the content of apps needs to be delivered in local languages and reflect local cultures. “The notion that you can take an intervention and just plop it down in a region where people might not even use the same terms for mental health as you're using is a little unrealistic,” says Ben-Zeev. “What we might call 'hearing voices' in the United States might be something like 'communicating with your elders' in a different region, depending on what label people attach to that experience.” At this point, the notion that apps can deliver quality health care in low-income regions remains largely theoretical. “This is generally where the mHealth field is,” says Natalie Leon, a scientist at the South African Medical Research Council in Cape Town. “It's a promise of potential effectiveness.” To make good on that promise, apps will have to be tested. Between 2013 and 2015, the number of mobile-health trials registered on ClinicalTrials.gov more than doubled, from 135 to 300. And the number of trials specifically focused on mental and behavioural health increased by 32%, according to a report by the IMS Institute for Health Informatics in Parsippany, New Jersey. One digital health company that has earned praise from experts is Big Health, co-founded by Colin Espie, a sleep scientist at the University of Oxford, UK, and entrepreneur Peter Hames. The London-based company's first product is Sleepio, a digital treatment for insomnia that can be accessed online or as a smartphone app. The app teaches users a variety of evidence-based strategies for tackling insomnia, including techniques for managing anxious and intrusive thoughts, boosting relaxation, and establishing a sleep-friendly environment and routine. Before putting Sleepio to the test, Espie insisted on creating a placebo version of the app, which had the same look and feel as the real app, but led users through a set of sham visualization exercises with no known clinical benefits. In a randomized trial, published in 2012, Espie and his colleagues found that insomniacs using Sleepio reported greater gains in sleep efficiency — the percentage of time someone is asleep, out of the total time he or she spends in bed — and slightly larger improvements in daytime functioning than those using the placebo app15. In a follow-up 2014 paper16, they reported that Sleepio also reduced the racing, intrusive thoughts that can often interfere with sleep. The Sleepio team is currently recruiting participants for a large, international trial and has provided vouchers for the app to several groups of independent researchers so that patients who enrol in their studies can access Sleepio for free. “We think this is the way forward for digital health,” says Espie. Mobile-phone-based treatments, he says, “should be tested and judged like any other intervention. We shouldn't treat people's health with any less respect because the treatment is coming through an app.”
When he was a teenager, Lee Gonzales could not save his uncle from a heroin overdose. Now he worries that the same drug could kill him after he gets out of jail. As Gonzales remembers, he had rousted his uncle from previous heroin stupors by propping him up and splashing water on his face. But there was no one around to help that day. And there was nothing available like the bright orange prescription bottle the 32-year-old heroin addict held in his hand on a recent morning. "This is enough medicine to save somebody, huh?" Gonzales said, fiddling with the nasal inhaler as a doctor sat with him in a cinderblock interview room in Denver's downtown jail. Similar scenes are unfolding in a growing number of jails and prisons across the country as health officials train soon-to-be-released inmates to use the overdose-reversal drug naloxone to save others and sometimes themselves. Dr. Joshua Blum teaches inmates about the nasal spray, which can undo the effects of an opiate overdose almost instantly. Blum told Gonzales, who was jailed on theft warrants, he could take the antidote with him when he is freed. "I think it's a great idea," Gonzales said. Naloxone, also known by the brand name Narcan, has become a key tool in curbing overdoes resulting from the nation's opioid abuse epidemic. The class of drug that includes prescription painkillers and heroin was involved in a record 28,648 deaths in 2014, and opioid overdoses have more than quadrupled since 2000, according to the Centers for Disease Control and Prevention. Recently released inmates are particularly vulnerable. Naloxone supporters say the opportunity to save potentially thousands of lives outweighs any fears that the promise of a nearby antidote would only encourage drug abuse. Officials already widely distribute the drug to police, paramedics, drug users and their families. The push to equip inmates is new, fueled by research showing former prisoners in Washington state were nearly 13 times more likely to die of an overdose in the two weeks after their release than other people. Heroin tolerance goes down while users abstain behind bars, but they often return to their previous dose when they get out, putting them at greater risk. "They're very anxious. They are released to environments where they have a lot of exposure to drugs. They are triggered to use, and they may not have support systems to help them," said Dr. Ingrid Binswanger, senior investigator for Kaiser Permanente Colorado's Institute for Health Research, who worked on the study. Researchers also found that 8 percent of overdose deaths in Washington state were former prisoners. Inmates set to be released from San Francisco's county jail have been offered naloxone kits since the program started there in March 2013. More than 1,700 inmates in six New York state prisons have been trained to use the antidote, and at least 600 have taken kits with them on their way out. And in Colorado, several county jails began giving certain inmates rescue kits in January, funded in part by the state's recreational marijuana taxes. It's hard to say what happens to the inmates given the drug after they're released, partly because reporting overdoses or reversals is voluntary. A study of 100 Rhode Island inmates who received naloxone found they were able to successfully administer the drug after being released. A few used it to reverse their own overdoses, said Dr. Jody Rich, an epidemiologist and director of the Center for Prisoner Health and Human Rights. The research did not track what happened to the inmates over time. "I wouldn't predict that it would stop people from using, and conversely it wouldn't encourage them to use," Rich said. In New York, two former prisoners have come forward to report three overdose reversals, said Sharon Stancliff, medical director of the Harm Reduction Coalition, which runs the training. One of those former inmates now helps train other prisoners to use naloxone. The King County jail in Washington state has trained 221 inmates, 10 of whom reported lifesaving reversals. Officials only learned of those successes when inmates returned to jail, public health spokesman James Apa said. Blum, a doctor at Denver Health Medical Center, took inmates' phone numbers so doctors could reach out to each of them six months after their release. The Colorado program is too new to have yielded quantifiable results. "We're telling this group of people that is highly stigmatized and not well-liked that they're good enough citizens that they might be able to go out and save a life," Stancliff said. "It's empowering." Naloxone is not addictive and does not cause a high. Big pharmacy chains like Walgreens and CVS now sell the antidote, also available as an injection, over the counter. And the Obama administration in February proposed $90 million more in federal spending for programs that help states and local governments to, among other aims, improve access to naloxone. Critics say it provides only temporary relief without combatting drug use. Maine Gov. Paul LePage, for example, has consistently opposed efforts to make the drug more accessible, saying that giving the antidote to family members of drug users would discourage people from seeking treatment. Blum acknowledged that naloxone isn't a cure. But overdose reversals can offer a chance to seek more comprehensive treatment, he said. Gonzales agreed to let his cellmates know about the drug and pledged to give it to friends and family when he gets out. And he recalled his own efforts to revive his uncle. "I wish I had that at the time when that all happened," he said. "I sure wish I did."