Body

Visiting a crowded pediatric emergency department in Canada may increase the likelihood of being hospitalized but is not linked to delayed hospitalization or death in children, according to research in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/lookup/doi/10.1503/cmaj.181426

Emergency department overcrowding is a problem in North America and has been associated with increased illness, death and lower patient and physician satisfaction.

"Although we found no significant association between overcrowding and hospital admission within 7 days or death within 14 days after discharge from hospital, we saw an increase in admissions among the sicker children and in return visits from kids who were less sick, with increasing degree of crowding" says Dr. Quynh Doan, BC Children's Hospital, and research director, Pediatric Emergency Medicine, University of British Columbia, Vancouver, BC.

The multicentre study analyzed more than 1.9 million pediatric emergency department visits at 8 hospitals in British Columbia, Alberta, Manitoba and Ontario over 5 years between 2010 and 2014.

"Possible explanations include a delay in timely initiation of medical interventions that could lead to deterioration requiring hospital admission; alternatively, clinicians may respond to emergency department crowding with rising levels of caution in their disposition decision-making," write the authors.

In a related commentary http://www.cmaj.ca/lookup/doi/10.1503/cmaj.190610, Drs. Alexander Moylan and Ian Maconochie, Department of Emergency Medicine, Imperial College Healthcare NHS Trust, United Kingdom, write, "there is no evidence that the trend of increasing attendances at pediatric emergency departments is reversing."

"Research into tools such as evidence-based early warning systems to support departments in providing safe care in the most demanding situations must support efforts to adapt to this challenge," the commentary authors conclude.

"The impact of pediatric emergency department crowding on patient and health care system outcomes: a multicentre cohort study" is published June 10, 2019.

Researchers in the UK developed a computer-aided National Early Warning Score (cNEWS) to determine if it could enhance the accuracy of predicting sepsis.

"The main advantage of these computer models is that they are designed to incorporate data that exist in the patient record, can be easily automated and place no extra burden on the hospital staff to collect additional information," says Professor Mohammed A. Mohammed, University of Bradford, Bradford, United Kingdom.

The cNEWS score can trigger screening for sepsis usually within 30 minutes of admission once routinely collected information has been electronically entered into the patient's medical record.

"These risk scores should support, rather than replace, clinical judgment. We hope they will heighten awareness of sepsis with additional information on this serious condition," says Professor Mohammed.

cNEWS may now be introduced carefully into hospitals with appropriate information technology infrastructure and evaluated.

"Computer-aided National Early Warning Score to predict the risk of sepsis following emergency medical admission to hospital: a model development and external validation study" is published April 8, 2019.

Philadelphia, June 10, 2019 - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that leads to significant health issues as well as high treatment costs. In this themed issue of Clinical Therapeutics, published by Elsevier, experts review multiple aspects of RA detection and intervention with the overall goal of moving the field closer to developing effective preventive measures. Identifying people before they develop the disorder could significantly alter the course of disease and spare people its damaging effects.

RA affects around one percent of the population worldwide. It leads to swollen, painful joints and can also damage other body systems such as the skin, eyes, lungs, heart, and blood vessels. This debilitating disease results in diminished quality of life, loss of work, pain, and suffering. It is also largely a "forever" disease from which patients with full-blown RA will suffer for the rest of their lives. While medications can control RA for many patients, very few experience a complete cure and are able to discontinue treatment. RA is an expensive disease. In the United States it currently costs around $20,000-30,000 per patient annually for treatment.

Guest-edited by Kevin D. Deane, MD, PhD, Associate Professor of Medicine, Division of Rheumatology, Department of Medicine University of Colorado Denver School of Medicine, Denver, CO, USA; and Tsang Tommy Cheung, MBBS (HK), Clinical Assistant Professor, Department of Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, this themed issue taps into the expertise of many scientists across the world and discusses multiple aspects of RA prevention. "These discussions will hopefully provide insights into how we can move RA forward to the point where we are preventing disease and also give guidance on how other autoimmune diseases could be prevented as well," explain the Guest Editors.

Many studies are already underway to learn how to prevent RA, however, prevention of autoimmune diseases is still new territory and there is a lot to discuss and learn. "Most people are familiar with prevention for diseases such as diabetes, heart disease, or cancer," notes Dr. Deane. "For example, it is very common for someone to have routine blood tests, which might reveal high cholesterol, a potential risk factor for a future heart attack. That individual can then implement lifestyle changes like more healthful eating, smoking cessation, and more exercise, or taking a medication to lower the risk of a future heart attack. We developed these approaches for heart attack prevention through clinical trials. The RA community has learned from these approaches and similar prevention-type trials are now underway in RA."

"Most autoimmune diseases are only identified once an individual gets 'sick.' For example, with RA, once someone has painful, swollen joints," adds Dr. Cheung. "Blood-based tests can now identify individuals who are at risk before they feel sick, opening a whole new world of screening and possible prevention. Treating RA very early may allow for cheaper, safer therapies to work because once full-blown RA has developed, typically very powerful medications are needed to control disease."

In a Commentary on the clinical burden of RA, John M. Davis III, MD, MS, Associate Professor of Medicine, Division of Rheumatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA, makes the case that preventive approaches would greatly benefit RA patients. "There have been great advances in the development of conventional synthetic, biologic, and targeted disease-modifying antirheumatic drugs (DMARDs) to treat RA as well as strategies to use these agents to control disease-associated inflammation to the state of either low disease activity or clinical remission," he comments. "However, with any given treatment strategy, up to 40-60 percent of patients ultimately respond inadequately. Investment in developing preventive strategies is expected to lead eventually to a paradigm shift from treating disease and disease-related complications to maintaining health of people worldwide."

The rigorously peer-reviewed articles in this themed issue cover topics such as the natural history of RA; nomenclature for the stages of development of RA; potential pharmacological targets; potential for prevention by targeting mucosal processes; predicting RA in at-risk individuals; optimal trial design for RA prevention studies; patient preferences; regulatory considerations; system challenges; monitoring safety; and adverse events. All of the authors contributed in a significant way to the overall picture of how RA prevention is developing.

The issue identifies several important challenges:

Getting society to invest in prevention, which requires that groups such as governments, the insurance industry, and pharmaceutical companies are also interested in prevention and willing to support it.

Finding prevention approaches that work - whether drugs or lifestyle changes (e.g., smoking cessation), or combinations of both.

Finding individuals who are at-risk for future RA through simple methods, which could be population-based blood testing or other approaches.

Getting the research and medical community to agree on the right terminology for RA. "Right now, RA is only applied once someone has arthritis. But it may be that we need to develop new terms like 'Pre-RA' that can be used to identify someone at high risk for future RA. For example, the term pre-diabetes is commonly used and is helpful for people to understand that they are in a stage of disease that indicates that they are at risk for getting worse unless they do something. We need similar terms in RA that can resonate with people, and help them take action," comments Dr. Deane.

Patient preference is also a major challenge. "Asking at-risk individuals to take medications with possible side effects when there is no clinically apparent disease is not easy at all," observes Dr. Cheung.

Many other rheumatic and autoimmune diseases follow a similar model as RA where there are blood markers that are abnormal, sometimes years before an individual feels "sick" from disease. These diseases include lupus, gout, and others such as vasculitis.

"RA science is in a fortunate situation compared to many other inflammatory diseases where it is rarely known when and where disease-specific immunity may be triggered and how it may gradually evolve towards targeting of the end organ," comments Lars Klareskog, MD, PhD, Rheumatology Unit, Department of Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden, in a Guest Editorial. "Research and solutions proposed in this issue may also serve as a demonstration example for many other chronic immune-mediated diseases."

Editor-in-Chief Richard Shader, MD, Tufts University School of Medicine, Boston, MA, USA comments, "The efforts of this team of experts to raise awareness of RA and to explore methods for early detection and intervention should catalyze the medical and scientific communities to increase their efforts to find better ways to treat and perhaps even prevent RA and its complications."

Prior research has already shown that the development of RA can be delayed with a single dose of medication that is typically used in people who have full-blown RA. That finding suggests that if individuals can be identified at the right time, future RA can be delayed or completely prevented. There are also multiple clinical trials underway that should help determine which drugs have the potential to prevent RA and who the best candidates are to receive this treatment.

"Treating RA very early may allow for cheaper, safer therapies to work because once full-blown RA has developed, typically very powerful medications are needed to control the disease. This is like stopping a fire when it is still at the stage of a candle - pretty easy. However, stopping a fire once a full-blow forest fire has developed is very hard!" conclude the Guest Editors.

Oakland, Calif. -- In a large new Kaiser Permanente study, children who were up to date on their pertussis vaccine schedule were far less likely to develop the disease than unvaccinated children. However, most pertussis cases were in fully vaccinated children. The risk of vaccinated children becoming ill increased with the time since vaccination, suggesting that waning effectiveness between doses was a significant contributor to recent outbreaks.

The study, "Acellular Pertussis Vaccine Effectiveness Over Time," was published on June 10 in the journal Pediatrics.

Pertussis, widely known as whooping cough, is a highly contagious and potentially life-threatening respiratory infection caused by the bacterium Bordetella pertussis. To help prevent it, the Centers for Disease Control and Prevention (CDC) recommends five doses of DTaP vaccine--a combination vaccine that protects against pertussis, diphtheria, and tetanus--between the ages of two months and six years.

"Most DTaP research has explored either vaccination status or waning effectiveness, but we looked at both at once," said Ousseny Zerbo, PhD, lead author of the new study and a staff scientist with the Vaccine Study Center at Kaiser Permanente Northern California's Division of Research.

Dr. Zerbo and his colleagues retrospectively analyzed the electronic health records of 469,982 children under the age of 11 who were members of Kaiser Permanente Northern California. Focusing on data from January 2006 through June 2017, they performed a series of statistical analyses to determine risk of pertussis according to vaccination status and time since a child's last dose.

The researchers found that risk of pertussis was 13 times higher for children who had never received DTaP than for children who were fully vaccinated with all recommended doses for their age. Under-vaccinated children--those who had received at least one dose but were behind schedule--were almost twice as likely to develop pertussis than were fully vaccinated children.

"However, for fully vaccinated children, we found that risk of pertussis increased as more time passed since their last dose," Dr. Zerbo said. Among age-appropriately vaccinated children between the ages of 19 months and 7 years the risk of pertussis was 5 times higher when they were more than 3 years from their last vaccine dose. Notably, most children diagnosed with pertussis in the study were up to date on DTaP. Of 738 pertussis cases, 603 were fully vaccinated, 99 completely unvaccinated, and 36 were partially vaccinated but behind schedule.

These findings suggest that in a US population where vaccine coverage is high, waning DTaP effectiveness is a significant driver of outbreaks, including the 2010 and 2014 outbreaks in California that each resulted in more than 9,000 pertussis cases.

"The big question has been whether pertussis outbreaks are due to under-vaccination, as in other diseases like measles, or to waning immunity," said Nicola P. Klein, MD, PhD, senior study author and director of the Vaccine Study Center. "The answer is that both factors matter."

More research is needed to quantify the relative roles of vaccine waning and under-vaccination in pertussis outbreaks. Still, the new findings point to the need for a better vaccine that lasts longer between doses. Meanwhile, the authors emphasize that families and clinicians should continue vaccinating children according to the CDC's recommended schedule.

The researchers emphasize that those vaccinated had lower rates of pertussis than those not vaccinated at all.

"Despite increased media attention on parents choosing not to vaccinate, children in our study had high coverage, which was not completely surprising," Dr. Zerbo said. One percent of the children with pertussis were unvaccinated, and 3 percent were under vaccinated. "We need to continue to encourage vaccination, no doubt about it," he said.

This study builds on a growing body of research from the Vaccine Study Center beginning with a 2012 study in New England Journal of Medicine which found that protection against pertussis after 5 DTaP doses wanes rapidly among school age children who had only ever received DTaP vaccines. This was followed by 2016 and 2017 studies in Pediatrics, one which showed that the routine adolescent Tdap booster also wanes rapidly, and one which showed that Tdap given to pregnant women was highly effective in preventing pertussis in newborns.

Key takeaways:

Lowering blood pressure, reducing sodium intake, and eliminating trans fat could prevent 94 million early deaths around the world.

Although scaling up the three interventions globally presents a major challenge, they are both achievable and affordable.

Boston, MA - A worldwide effort to lower people's blood pressure, cut their sodium intake, and eliminate trans fat from their diet could dramatically reduce the incidence of premature death from cardiovascular disease (CVD) over a quarter century, according to a new study led by Harvard T.H. Chan School of Public Health.

"Focusing our resources on the combination of these three interventions can have a huge potential impact on cardiovascular health through 2040," said lead author Goodarz Danaei, associate professor of global health at Harvard Chan School.

The study will be published online June 10, 2019 in the journal Circulation.

Researchers used global data from multiple studies and estimates from the World Health Organization in making their calculations.

They estimated that scaling up treatment of high blood pressure to 70% of the world's population could extend the lives of 39.4 million people. Cutting sodium intake by 30% could stave off another 40 million deaths and could also help decrease high blood pressure, a major risk factor for CVD. And eliminating trans fat could prevent 14.8 million early deaths.

More than half of all delayed deaths, and two-thirds of deaths delayed before age 70, are projected to be among men, who have the highest numbers of noncommunicable disease deaths globally, researchers found. Regions expected to benefit most from the interventions include East Asia, the Pacific, and South Asia, as well as countries in sub-Saharan Africa.

The authors said that a variety of programs and policies would be necessary to reduce premature CVD-related deaths. One important strategy would be to increase the use of blood pressure medications, many of which are safe and affordable.

The researchers acknowledged that scaling up the three interventions would be a "huge challenge," requiring countries to commit additional resources to boost health care capacity and quality. But they added that previous analyses have shown that the interventions are achievable and affordable. For example, a Kaiser Permanente program in Northern California increased control of hypertension to 90% among thousands of the health system's patients between 2001 and 2013, using strategies such as improved treatment protocols, patient-friendly services, and healthcare information systems that facilitate tracking people with hypertension. Similar approaches have been adapted and tested in some low- and middle-income countries, leading to notable improvements in hypertension treatment and control, the authors said.

"These are realistic goals that have been shown to be attainable on smaller scales," said Danaei. "We need the commitment to scale up the programs to achieve them globally."

The first New Zealand-wide study of the burden of Legionnaire's disease has found triple the number of cases of this form of pneumonia than previously reported.

The study, led by University of Otago, Christchurch Professor David Murdoch, has just been published in the Lancet Infectious Diseases. It gives the first accurate picture of the burden of the disease in New Zealand, but has international implications as few places routinely test for the potentially deadly - and preventable - bacteria.

The researchers arranged for people hospitalised with pneumonia from almost all of New Zealand during one calendar year to have a specialised test that detects legionella bacteria. Three times the number of cases were diagnosed compared with the average number of cases confirmed over each of the previous three years.

Specifically, the researchers found:

Almost 60% of patients were aged over 65.

Nearly a third of confirmed cases lived in more socio-economically deprived areas.

Almost 80% of patients had been hospitalised at some time over the previous five years, but fewer than half (41%) had been hospitalised for respiratory disease.

High rates of the disease in areas which had previously reported low numbers of cases. Notably, the Bay of Plenty District Health Board area (more than 8 cases per 100,000 people) and the Hawkes Bay and the Waitemata (which both had between 6 and 8 cases per 100,000). Canterbury also had rates of between 6 and 8 cases per 100,000.

About two-thirds of cases were admitted to hospital during winter and spring.

Professor Murdoch, a clinical microbiologist and researcher, says a special test called the polymerase chain reaction (PCR) is the best way to diagnose Legionnaires' disease as chest x-rays or other tests cannot differentiate between this and other forms of pneumonia. The disease requires different treatments from other types of pneumonia. The sooner the infection is treated with bacteria-specific medication, the better the prognosis, he says.

"This research shows the incidence of Legionnaires' disease in New Zealand is much higher than previously identified. Indeed, we have the highest reported incidence in the world. The research also supports the routine use of the PCR test to detect and ensure access to appropriate treatments,'' Professor Murdoch says.

The results are relevant to other countries as the bacteria causing Legionnaires' disease is present internationally but few countries have routine testing in place, Professor Murdoch says.

The study identified the most common form of bacteria causing the disease in New Zealanders was Legionella longbeachae (in 63% of cases). This strain is found in soil and composted plant material, and people at greatest risk are those involved in gardening activities.

To get their results, the research team tested all respiratory samples from patients with pneumonia admitted to any of the 20 participating hospitals between May 2015 and May 2016. During the year a total of 238 cases were identified, or 5.4 cases per 100,000 New Zealanders. This was three times the rate expected based on the number of people diagnosed in the preceding three years. Of the 238 cases, 15 died within 90 days of diagnosis and 38 cases required treatment in an intensive care unit (ICU).

Professor Murdoch says the research was possible because of the involvement of staff and laboratories from 20 hospitals and 17 different District Health Boards. It is unusual for this degree of collaboration on research projects, he said.

A new study published in PLoS Medicine found that the adoption of the World Health Organization's 2015 "Treat All" recommendation was followed by large increases in rapid initiation of antiretroviral therapy (ART) in six sub-Saharan African countries.

The study found significant increases in rapid ART initiation immediately after national introduction of Treat All policies in Burundi, Kenya, Malawi and Rwanda, with 12.5 to 34.5 percentage point increases in the percentage of patients who initiated ART within 30 days of enrolling into HIV care. Although no significant change in rapid ART initiation was observed immediately following national adoption of Treat All in Uganda and Zambia, rates of rapid ART initiation in these countries increased significantly in the months following policy introduction. Overall, across the six countries, 81.6 percent of patients enrolling into care following national adoption of Treat All policies initiated treatment within 30 days of enrollment.

Led by Olga Tymejczyk of the Institute for Implementation Science in Population Health (ISPH) at the CUNY Graduate School of Public Health and Health Policy (CUNY SPH), the study used a quasi-experimental regression discontinuity design to assess the impact of national Treat All policies, with data from 814,603 patients enrolling into HIV care in the six study countries, part of the IeDEA research collaboration. Using real-world patient data, primarily from public sector health facilities, study findings suggest that national adoption of the WHO's Treat All recommendation has led to appreciable increases in rapid ART initiation.

This study is an early indication that Treat All policies for HIV can dramatically increase access to services in low resource settings with high HIV prevalence. The researchers emphasize, however, that as more follow-up data become available, it will be important to assess whether patients starting treatment under national Treat All policies remain on treatment and achieve viral suppression. Dr. Denis Nash, Professor of Epidemiology at CUNY SPH and the study's senior author, also stressed that Treat All policies need to be accompanied by effective testing programs that get people diagnosed early and linked to care without delay.

"This study hails the beginning of an important new era in the response to the HIV epidemic in sub-Saharan Africa," says Nash. "At a time where there has been talk about reducing US funding for the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) and the Global Fund--the primary source of funding for HIV treatment and prevention in many of the hardest hit areas of the world--it is critical to sustain our investments in HIV prevention and treatment, rather than back off. With the adoption of national Treat All policies, there is real potential to dramatically reduce new HIV infections and HIV-related deaths, and to end the HIV epidemic."

A new study led by Boston University School of Public Health (BUSPH) researchers finds that there is no consistent association between consuming iron and becoming pregnant. The study, published in The Journal of Nutrition, finds that heme iron, which mostly comes from meat, has no effect on how long it takes a woman to conceive, while non-heme iron, which is found mainly in vegetables and dietary supplements, has a modest effect only for women who are more likely to be iron-deficient because of heavy menses or having previously given birth.

"For the average pregnancy planner, it is probably wise to take a preconception multivitamin, but more for the folic acid than for the iron content," says study senior author Dr. Elizabeth Hatch, professor of epidemiology at BUSPH. "If you have extremely heavy menstrual cycles, it might be a good idea to have your iron status checked by your healthcare provider."

Hatch and her colleagues analyzed data from two prospectively-studied cohorts of women who were trying to conceive: 2,969 North American women in the BUSPH-based PRESTO study and 1,693 Danish women in the Snart Foraeldre study. In both cohorts, participants completed questionnaires every eight weeks for one year or until they conceived. The researchers estimated heme and non-heme iron intake from the questionnaire responses about diet and about dietary supplement use.

The researchers found no association between a woman's intake of heme iron and the number of cycles it took for her to conceive. However, consuming more non-heme iron (both from dietary supplements and from food) was associated with a slightly increased chance of pregnancy in women who had previously given birth. In the PRESTO cohort, non-heme iron intake was also associated with a slightly increased chance of conception among women who had heavy menses or short menstrual cycles.

PHILADELPHIA - White coat hypertension, a condition in which a patient's blood pressure readings are higher when taken at the doctor's office compared to other settings, was originally attributed to the anxiety patients might experience during medical appointments. However, over the years, research has suggested the elevated readings might be a sign of underlying risk for future health problems. A new study led by researchers from Penn Medicine, published today in the Annals of Internal Medicine, revealed that patients with untreated white coat hypertension not only have a heightened risk of heart disease, but they are twice as likely to die from heart disease than people with normal blood pressure.

Researchers also found that patients with white coat hypertension who were taking medication to treat their high blood pressure, called antihypertensives, did not have an increased risk of heart disease or cardiovascular-related death compared to those with normal blood pressure readings.

"Studies suggest that about one in five adults may have white coat hypertension. Our findings underscore the importance of identifying people with this condition," said the study's lead author Jordana B. Cohen, MD, MSCE, an assistant professor in the division of Renal-Electrolyte and Hypertension and a senior scholar in the Center for Clinical Epidemiology and Biostatistics. "We believe individuals with isolated in-office hypertension - those who are not taking blood pressure medication - should be closely monitored for transition to sustained hypertension, or elevated blood pressure both at home and the doctor's office."

High blood pressure, or hypertension, is a defined as a top reading of at least 130 or a bottom one of 80. The condition affects nearly a third of American adults and, if left untreated, increases one's risk for severe complications, including heart attack and stroke. To diagnose and manage the condition, recent hypertension guidelines strongly recommend out-of-office blood pressure monitoring, such as at-home monitoring and ambulatory blood pressure monitoring, which requires patients to wear a portable device that records blood pressure readings over a 24-hour period. However, providers have been slow to adopt this practice due, in part, to skepticism over the usefulness of screening for white coat hypertension given the inconsistent findings - from past studies - and uncertainty around its association with heart disease and death.

To identify the cardiovascular risks of white coat hypertension, the researchers conducted a meta-analysis of 27 studies, comprising more than 60,000 patients, that evaluated the health risks associated with the condition. They found that patients with untreated white coat hypertension had a 36 percent increased risk of heart disease, 33 percent increased risk of death and 109 percent increased risk of death from heart disease.

"Our findings support the pressing need for increased out-of-office blood pressure monitoring nationwide, as it's critical in the diagnosis and management of hypertension," Cohen said. "Simultaneously, we advise individuals with untreated white coat hypertension to engage in lifestyle modifications, including smoking cessation, reduction in their alcohol intake, and making improvements to their diet and exercise regimens. We also caution providers not to over-treat individuals with white coat hypertension who are already on blood pressure medication, as this could lead to dangerously low blood pressures outside of the office and unnecessary side effects from medication."

Researchers noted that future studies are needed to investigate interventions to reduce the cardiac risk of white coat hypertension.

This work was supported, in part, by a grant from the National Institutes of Health (K23-HL133843). Additional Penn authors on the study include Matthew G. Denker, Debbie L. Cohen and Raymond R. Townsend.

Doctors have urged hospitals around the world to reconsider the type of fluids used to treat children gravely ill with sepsis.

In a new study, researchers from Imperial College London found saline fluids commonly used to help stabilise critically ill children may trigger the blood to become more acidic, and lead to organ failure.

The team, who published their work in The Lancet Respiratory Medicine, urge hospitals across the UK - and the world - to consider swapping saline fluids for a different type of so-called buffered solution that helps prevent the blood becoming too acidic.

Although the research studied data from over 3000 children with malaria or sepsis (blood poisoning triggered by severe infection) in Africa, the research team say the findings could apply to all critically ill children and adults.

When a critically ill patient is brought into hospital, medical teams often give the patient very large amounts of fluid rapidly into their vein through a drip. This is called a fluid 'bolus', and helps increase their blood pressure and heart rate, and ensure blood is still pumped around the body.

The fluids most commonly used in hospitals around the globe are called saline (a type of salt water), or 5% albumin (a saline solution that contains albumin protein).

These fluids were always assumed to be the most effective at stabilising a patient, until an Imperial College-lead 2011 trial of 3000 children - called the FEAST trial - suggested otherwise. The trial, conducted in Kenya, Uganda and Tanzania, compared rapidly giving a bolus of saline or 5% albumin, to giving much smaller amounts of fluid over a longer period of time.

The research team hoped the trial would reduce the number of the child deaths from infection, but were shocked to find giving a large fluid bolus was associated with a higher death rate. An independent panel decided to stop the trial early, while pointing out that children in the trial still had a better chance of survival than is normally the case in Africa, in part due to extra training given to hospital staff.

In the latest study, the scientists wanted to investigate why the saline fluids were associated with a higher risk of death, and if these findings could apply to other children around the world.

By analysing the data from the FEAST trial, and comparing this with data from over 18,000 children who attended a UK hospital and other hospitals in Malawi and South Africa, the team found that the use of saline or 5% albumin had a number of adverse effects.

The research, funded by the Medical Research Council, Department for International Development, and the National Institute for Health Research Imperial College Biomedical Research Centre, found that although the fluid bolus did improve heart rate and blood pressure, the solution also harmed lung function, and increased brain swelling and acidity of the blood - which together contributed to the increased mortality observed in the FEAST trial.

The researchers stress that fluids are still a vital part of resuscitation, and these findings apply mainly to critically ill patients. They say saline and 5% albumin may have less adverse effects in moderately ill patients, but suggest solutions that contain buffering components, and less chloride (which can cause blood to become acidic), should be used in gravely ill individuals.

The team add that much of the FEAST data came from children who did not have access to an intensive care unit - and therefore the chance of a fluid bolus increasing the chance of death is much smaller in settings with comprehensive medical facilities. But they add that even in these conditions, the use of a bolus of saline or 5% albumin could still worsen a child's condition.

They say further trials are now urgently needed to investigate the use of alternative fluids that contain buffers and less chloride, as well as how much of the fluid to use.

Professor Michael Levin, from the Department of Medicine at Imperial College London, who led the study, explained: "This study suggests we need a re-think of how we resuscitate patients - what volume of fluid we give to patients, and the type of fluid we give to patients.

"The FEAST trial provided the first clear evidence that administration of a rapid 'bolus' of normal saline or albumin to critically ill patients was harmful if advanced intensive care support was not available. Our new analysis has identified the mechanisms through which fluid bolus caused harm. Although the bolus fluids had the desired effect in improving cardiovascular function, this came at the cost of a range of unexpected adverse effects including worsening lung function, increased brain swelling and most importantly the blood becoming more acidic.

"The effect of high chloride fluids like normal saline and 5% albumin on blood acidity can be prevented by using alternative fluids that are lower in chloride concentration. Trials are now needed to establish whether alternative resuscitation fluids, used in smaller amounts, can achieve the beneficial effects on cardiovascular function without the adverse effects on lungs, brain and blood acidity."

Dr Aubrey Cunnington, a co-author of the study from Imperial's Department of Medicine, added: "The findings and implications of the FEAST trial have perplexed the medical community. Uncertainty about the mechanisms by which fluid bolus increased mortality in FEAST is probably one of the main reasons why the trial findings have not resulted in as many changes in international guidelines as might be expected. We found evidence that normal saline or 5% albumin fluid boluses worsened the function of multiple organs in the body."

Professor Simon Nadel, a further co-author from Imperial's Department of Medicine, and consultant in Paediatric Intensive Care at Imperial College Healthcare NHS trust said: "The FEAST study showed definitively for the first time that rapid fluid administration led to a higher mortality in children who were already seriously ill, than slower fluid administration. It has to be emphasised that this finding occurred in an environment where there was no access to advanced intensive care support.

It is now clear that we have to be aware of the rate and type of fluid resuscitation for critically ill patients, and it is vital that properly conducted studies into the most appropriate fluid resuscitation in the critically ill patient are carried out as soon as possible."

A set of clinical trials examining youth and adults with type 2 diabetes or impaired glucose tolerance has found that disease progression in adults slowed during medical treatment but resumed after treatment stopped. Youth on the same treatment had markedly poorer outcomes with continued disease progression both during and after the treatment. This research, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was published June 9 in the journals Diabetes and Diabetes Care and presented at the American Diabetes Association Scientific Sessions in San Francisco. NIDDK is part of the National Institutes of Health.

The Restoring Insulin Secretion (RISE) Adult and Pediatric Medication Studies compared the use of different treatments among adults aged 20-65 and youth aged 10-19 with impaired glucose tolerance or early onset type 2 diabetes with the aim of preserving beta cell function - key to the body's ability to make and release insulin.

In the adult study, participants were randomly assigned to receive either long-acting insulin (glargine) for three months followed by nine months of metformin, the drug liraglutide in combination with metformin for 12 months, metformin alone for 12 months, or a placebo. Researchers wanted to see whether early aggressive treatment could have a lasting effect on slowing or stopping the decline of beta cell function that occurs in people with type 2 diabetes. Participants were monitored for three additional months after treatments ended.

Results showed that adult participants had improvements in beta cell function and blood glucose control while on the treatments, with those in the liraglutide plus metformin group showing the most improvement after 12 months. However, these improvements did not persist among any of the groups after treatment ended.

"The RISE medication studies show that these treatments for type 2 diabetes do not make lasting changes to beta cells," said study chair Dr. Steven Kahn from the Veteran's Affairs Puget Sound Health Care System and University of Washington School of Medicine. "For adults, we saw that the treatment options were equally effective while people were actively on them - but people need to stay on treatment to maintain the benefits."

In a companion paper, findings from the adult study were compared to those from the RISE Pediatric Medication Study published in 2018, which showed that beta cell function declined in the two youth treatment groups during active treatment, and worsened after treatment ended.

The RISE Adult and Pediatric Medication Studies were designed together to enable direct comparison of the effect of treatment on youth and adults. The youth study compared the use of three months of insulin glargine followed by metformin for nine months to metformin alone for 12 months. Insulin glargine and metformin are the only U.S. Food and Drug Administration-approved medications for youth with type 2 diabetes.

"Though the medications' effectiveness for adults while on treatment is reassuring, the poor results for youth in the study, both during and after treatment, underscore the continued urgent need for new approaches to prevent and treat type 2 diabetes in youth, since the disease progresses more rapidly given the same treatment as adults," said Dr. Ellen Leschek, a study author and the NIDDK project scientist for RISE.

This close comparison between adults and youth receiving the same type 2 diabetes treatments supports earlier research suggesting the disease is more aggressive in youth than adults, and points to new areas of research that may help explain why.

"The RISE studies show that type 2 diabetes affects youth differently, and more aggressively, than adults, said NIDDK Director Dr. Griffin P. Rodgers. "These findings demonstrate the need for continued research to identify new treatment strategies to control and treat type 2 diabetes, and underscore the need to focus on prevention efforts, especially for youth."

Baltimore (June 9, 2019) - The foods and nutrients a woman consumes while pregnant have important health implications for her and her baby. Nutrition 2019, the annual meeting of the American Society for Nutrition, will feature new research on prenatal vitamins, infant supplements and the impacts of a mother's diet during pregnancy and after the baby is born.

Nutrition 2019 is being held June 8-11, 2019 at the Baltimore Convention Center. Contact the media team for more information or to obtain a free press pass to attend the meeting.

Studies examine dosage and labeling of common supplements

Many prenatal supplements contain too much folic acid
Consuming folic acid prior to pregnancy helps prevent birth defects. But a new study found most prenatal supplements were labeled as containing more folic acid than the current recommended daily intake. The study also revealed different agencies and scientific bodies provide conflicting messaging around the optimal intake of folic acid (from supplements) and folate (from food) during pregnancy. Nancy Potischman, National Institutes of Health, will present this research on Sunday, June 9, from 1:45 - 2:45 p.m. in the Baltimore Convention Center, Halls A-B (poster #268) (abstract).

Prenatal vitamins often have nutrient content higher than labeled
Chemical analysis of the contents of 24 prenatal multivitamins representing about 60 percent of the prenatal multivitamin products sold through U.S. pharmacies in 2015-2016 revealed that most contained greater quantities of vitamins and minerals than was declared on the label, perhaps to account for possible losses during storage. The greatest difference was seen for vitamin D, with supplements containing an average of 29 percent more vitamin D than was indicated on product labels. By offering a more accurate picture of supplements' contents, the findings can help scientists who study the impacts of nutrients on health outcomes, researchers say. Karen W. Andrews, U.S. Department of Agriculture, will present this research on Sunday, June 9, from 4:45 - 5:00 p.m. in the Baltimore Convention Center, Room 317 (abstract).

Vitamin D supplementation improves babies' growth
Babies born with low stores of vitamin D can have problems with bone growth, and the American Academy of Pediatrics recommends children get at least 400 International Units of the vitamin each day. In a recent clinical trial, newborns with low vitamin D stores who were given a higher dosage (1,000 IU/day) of vitamin D supplementation more rapidly built up their stores and gained more lean body mass by six months of age compared to those given the standard of care (400 IU/day). Compared to a group of infants born with very good vitamin D stores, the babies receiving the 1,000 IU/day intervention appeared to have normal lean mass. Maryam Razaghi, McGill University, will present this research on Monday, June 10, from 12:45 - 1:45 p.m. in the Baltimore Convention Center, Halls A-B (poster #301) (abstract).

Insights on staying healthy when you're 'eating for two'

Evidence that eating well before pregnancy lowers risk of preeclampsia
While scientists aren't sure what causes the dangerous pregnancy complication preeclampsia, or how to prevent it, a new study suggests diet plays a role. Among more than 20,000 pregnancies, researchers found women who followed a healthier diet before getting pregnant were significantly less likely to develop preeclampsia. Diet quality was assessed based on adherence to the American Heart Association dietary recommendations and the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. Mariel Arvizu, Harvard T.H. Chan School of Public Health, will present this research on Tuesday, June 11, from 11:45 a.m. - noon in the Baltimore Convention Center, Room 317 (abstract).

New insights on pregnancy and obesity
Obesity before pregnancy increases the risk of some health problems for a pregnant woman and her baby, but current recommendations to minimize these risks do not differentiate between mild and severe obesity. A new study of more than 25,000 women found those with more severe obesity gained less weight during pregnancy, but had larger babies, than those with less severe obesity. These results suggest the risks and optimal management of obesity during pregnancy may vary depending on severity. This study also found only one in five obese women gained the recommended amount of weight during pregnancy while 60 percent gained excessive weight. Amy R. Nichols, The University of Texas at Austin, will present this research on Monday, June 10, from 12:45 - 1:45 p.m. in the Baltimore Convention Center, Halls A-B (poster #227) (abstract).

For patients with diabetes, bringing down and maintaining lower blood glucose levels is important to minimize the risk of long-term complications such as nerve damage, kidney damage, an increased risk of heart disease, eye problems, and more. Through a randomized, multicenter clinical trial sponsored by Novo Nordisk, investigators studied blood glucose results for patients assigned to either take insulin (insulin glargine, IGlar U100) or insulin degludec plus liraglutide (IDegLira), a combination of both insulin and an additional medication to help with blood sugar control. The global study team found that participants who received IDegLira were better able to achieve blood glucose goals and remain at that goal longer compared to those assigned to receive IGlar. Results are presented today at the American Diabetes Association's Scientific Sessions and published simultaneously in The Lancet Diabetes & Endocrinology.

"We believe this reflects a more durable effect of IDegLira compared to IGlar, possibly related to the complementary roles and physiologic effects in the combination formulation," said corresponding author and global signatory investigator Vanita R. Aroda, MD, a specialist in the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women's Hospital.

The study, known as DUAL VIII (Durability of insulin degludec plus liraglutide versus insulin glargine U100 as initial injectable therapy in type 2 diabetes) was a 104-week international, multicenter, open-label, phase 3b trial. It enrolled 1,012 patients who were insulin-naïve, aged 18 and older, and had HbA1c 7-11% and a BMI of 20 kg/m² or higher on stable doses of oral antidiabetic drugs. Patients were randomly assigned to take insulin glargine 100 units/mL (IGlar U100) or IDegLira, which contains a GLP-1 receptor analogue -- a molecule that is similar to a naturally occurring compound that reduces blood glucose levels. Both IDegLira and IGlar were administered as once-daily injections. The primary endpoint was time to need for treatment intensification.

Patients in the IDegLira group had significantly longer time until need for intensification of treatment than those in the IGlar group. Investigators reported more effective glucose lowering, less weight gain and less risk of hypoglycemia, or low blood sugar, over the 104 weeks with the combination approach (IDegLira) compared to basal insulin alone (IGlar). No new safety or tolerability issues were reported in the trial.

In their paper, Aroda and her colleagues describe the clinical inertia that surrounds the treatment of diabetes. Concerns about weight gain, low blood sugar and fear of injectables may prevent patients from achieving better glycemic control. Although both IDegLira and IGlar were given as daily injections, IDegLira showed improved outcomes without the need for a separate, additional injection.

"IDegLira showed greater durability than IGlar U100 in reaching and maintaining patients at glycemic goals for longer, thereby minimizing the need for additional therapy, while also reducing the side effects often associated with insulin-only therapy," the authors write. "Taken together, the data from DUAL VIII illustrate the potential benefit of a combined insulin plus GLP-1RA approach, such as IDegLira, as a first injectable therapy."

Baltimore (June 8, 2019) - Preliminary findings from a new study reveal that inadequate fruit and vegetable consumption may account for millions of deaths from heart disease and strokes each year. The study estimated that roughly 1 in 7 cardiovascular deaths could be attributed to not eating enough fruit and 1 in 12 cardiovascular deaths could be attributed to not eating enough vegetables.

Low fruit intake resulted in nearly 1.8 million cardiovascular deaths in 2010, while low vegetable intake resulted in 1 million deaths, according to researchers. Overall, the toll of suboptimal fruit intake was almost double that of vegetables. The impacts were most acute in countries with the lowest average intakes of fruits and vegetables.

"Fruits and vegetables are a modifiable component of diet that can impact preventable deaths globally," said lead study author Victoria Miller, a postdoctoral researcher at the Friedman School of Nutrition Science and Policy at Tufts University. "Our findings indicate the need for population-based efforts to increase fruit and vegetable consumption throughout the world."

Miller will present the research findings at Nutrition 2019, the American Society for Nutrition annual meeting, held June 8-11, 2019 in Baltimore.

Fruits and vegetables are good sources of fiber, potassium, magnesium, antioxidants and phenolics, which have been shown to reduce blood pressure and cholesterol. Fresh fruits and vegetables also improve the health and diversity of good bacteria in the digestive tract. People who eat more of these foods also are less likely to be overweight or obese, lowering their risk of cardiovascular disease.

"Global nutrition priorities have traditionally focused on providing sufficient calories, vitamin supplementation and reducing additives like salt and sugar," said senior study author Dariush Mozaffarian, dean of the Friedman School of Nutrition Science and Policy at Tufts University. "These findings indicate a need to expand the focus to increasing availability and consumption of protective foods like fruits, vegetables and legumes--a positive message with tremendous potential for improving global health."

Based on dietary guidelines and studies of cardiovascular risk factors, the researchers defined optimal fruit intake as 300 grams per day, equivalent to roughly two small apples. Optimal intake of vegetables, including legumes, was defined as 400 grams per day, equivalent to about three cups of raw carrots.

The researchers estimated average national intakes of fruit and vegetables from diet surveys and food availability data representing 113 countries (about 82 percent of the world's population), then combined this information with data on causes of death in each country and data on the cardiovascular risk associated with inadequate fruit and vegetable consumption. The work is part of the Global Dietary Database project funded by the Bill & Melinda Gates Foundation.

Based on data from 2010, the scientists estimated that suboptimal fruit consumption results in nearly 1.3 million deaths from stroke and more than 520,000 deaths from coronary heart disease (narrowing of the heart's arteries) worldwide each year. Suboptimal vegetable consumption was estimated to result in about 200,000 deaths from stroke and more than 800,000 deaths from coronary heart disease.

The impact of inadequate fruit and vegetable intake was greatest in countries with the lowest fruit and vegetable consumption. Countries in South Asia, East Asia and Sub-Saharan Africa had low fruit intake and high rates of associated stroke deaths. Countries in Central Asia and Oceania had low vegetable intake and high rates of associated coronary heart disease.

In the United States, suboptimal vegetable intake may account for 82,000 cardiovascular deaths while suboptimal fruit intake accounted for 57,000 deaths. Cardiovascular disease is the number one cause of death in the United States and worldwide.

By age group, suboptimal fruit and vegetable intake had the greatest perceived proportional impact on cardiovascular disease deaths among younger adults. By gender, suboptimal fruit and vegetable intake had the greatest proportional impact on cardiovascular disease deaths in men, likely because women tend to eat more fruits and vegetables, Miller noted.

Victoria Miller will present this research on Saturday, June 8, at 9:35 a.m. in the Baltimore Convention Center, Poster Theater 1 (abstract). Contact the media team for images and more information or to obtain a free press pass to attend the meeting.

Researchers know that exosomes, tiny nanoparticles released from fat cells, travel through the bloodstream and body, regulating a variety of processes, from growth and development to metabolism. The exosomes are important in lean, healthy individuals in maintaining homeostasis, but when fat gets 'sick' - the most common reason for this is too much weight gain - it can change its phenotype, becoming inflammatory, and disrupts how our organs function, from how our skeletal muscle and liver metabolize sugar to how our blood vessels process cholesterol.

Robert J. Freishtat, M.D., M.P.H., the chief of emergency medicine at Children's National Health System and a professor of precision medicine and genomics at the George Washington University School of Medicine and Health Sciences, and Sheela N. Magge M.D., M.S.C.E., who is now the director of pediatric endocrinology and an associate professor of medicine at the Johns Hopkins School of Medicine, were curious about what this process looked like in teens who fell in the mid-range of obesity.

Obesity is a major risk factor for insulin resistance and type 2 diabetes, but Dr. Freishtat and Dr. Magge wanted to know: Why do some teens with obesity develop type 2 diabetes over others? Why are some teens in this mid-range of obesity metabolically healthy while others have metabolic syndrome? Can fat in obese people become sick and drive disease?

To test this, Dr. Freishtat and Dr. Magge worked with 55 obese adolescents, ages 12 to 17, as part of a study at Children's National. The participants - 32 obese normoglycemic youth and 23 obese hyperglycemic youth - were similar in age, sex, race, pubertal stage, body mass index and overall fat mass. The distinguishing factor: The hyperglycemic study participants, the teens with elevated blood sugar, differed in where they stored fat. They had extra visceral fat (or adipose tissue) storage, the type of fat that surrounds the liver, pancreas and intestines, a known risk factor for type 2 diabetes.

Dr. Magge and Dr. Freishtat predicted that circulating exosomes from the teens with elevated blood sugar are enriched for microRNAs targeting carbohydrate metabolism.

They used three tests to examine study participants' metabolism, body composition and circulating exosomes. The first test, an oral glucose tolerance test, measures how efficiently the body metabolizes sugar; the second test is the whole body DXA, or dual-energy x-ray absorptiometry, which analyzes body composition, including lean tissue, fat mass and bone mineral density; and the third test, the serum adipocyte-derived exosomal microRNA assays, is an analysis of circulating fat signals in the bloodstream.

They found that teens with elevated blood sugar and increased visceral fat had different circulating adipocyte-derived exosomes. These study participants' exosomes were enriched for 14 microRNAs, targeting 1,304 mRNAs and corresponding to 179 canonical pathways - many of which are directly associated with carbohydrate metabolism and visceral fat.

Dr. Magge will present this research, entitled "Changes in Adipocyte-Derived Exosomal MicroRNAs May Play a Role in the Progression from Obese Normoglycemia to Hyperglycemia/Diabetes," as an oral abstract at the American Diabetes Association's 79th Scientific Sessions on Saturday, June 8.

Dr. Freishtat envisions having this information will be especially helpful for a patient in a mid-range of obesity. Exosomes primarily consist of small non-coding RNAs. In the current study, the altered RNAs affect P13K/AKT and STAT3 signaling, vital pathways for metabolic and immune function.

"Instead of waiting until someone has the biochemical changes associated with type 2 diabetes, such as hyperglycemia, hyperlipidemia and insulin resistance, we're hoping physicians will use this information to work with patients earlier," says Dr. Freishtat. "Through earlier detection, clinicians can intervene when fat shows sign of illness, as opposed to when the overt disease has occurred. This could be intervening with diet and lifestyle for an obese individual or intervening with medication earlier. The goal is to work with children and teens when their system is more plastic and responds better to intervention."

As this research evolves, Dr. Freishtat continues to look at the intergenerational effects of circulating adipocyte-derived exosomes. Through ongoing NIH-funded research in India, he finds these exosomes, similar in size to lipoproteins, can travel across the placenta, affecting development of the fetus in utero.

"What we're finding in our initial work is that these exosomes, or 'sick' fat, cross the placenta and affect fetal development," Dr. Freishtat says. "Some of the things that we're seeing are a change in body composition of the fetus to a more adipose phenotype. Some of our work in cell cultures shows changes in stem cell function and differentiation, but what's even more interesting to us is that if the fetus is a female sex that means her ovaries are developing while she's in utero, which means a mother's adipocyte-derived exosomes could theoretically be affecting her grandchild's phenotype - influencing the health of three generations."

While this research is underway, Dr. Freishtat is working with JPOD @ Boston, co-located with the Cambridge Innovation Center in Cambridge, Massachusetts, to develop a test to provide analyses of adipocyte-derived exosomal microRNAs.

"It's important for families to know that these studies are designed to help researchers and doctors better understand the development of disease in its earliest stages, but there's no need for patients to wait for the completion of our studies," says Dr. Freishtat. "Reaching and maintaining a healthy body weight and exercising are important things teens and families can do today to reduce their risk for obesity and diabetes."

A novel class of radiopharmaceuticals has proven effective in non-invasively identifying nearly 30 types of malignant tumors, according to research published in the June issue of The Journal of Nuclear Medicine. Using 68Ga-FAPI positron emission tomography/computed tomography (PET/CT), researchers were able to image a wide variety of tumors with very high uptake and image contrast, paving the way for new applications in tumor characterization, staging and therapy.

The 68Ga-FAPI radiotracer targets cancer-associated fibroblasts, which can contribute up to 90 percent of a tumor's mass. Many cancer-associated fibroblasts differ from normal fibroblasts by their specific expression of the fibroblast activation protein, or FAP. FAP-specific inhibitors were first developed as conventional anticancer drugs; now they have been advanced into tumor-targeting radiopharmaceuticals.

In the retrospective study, researchers used PET/CT to image 80 patients with 28 different kinds of cancer, aiming to quantify 68Ga-FAPI uptake in primary, metastatic or recurring cancers. All patients were referred for experimental diagnostics by their treating oncologists because they were facing an unmet diagnostic challenge that could not be solved sufficiently with standard methods. The injected activity for the 68Ga-FAPI examinations was 122-312 MBq, and the PET scans were initiated one hour after injection. Tumor tracer uptake was measured by SUVmean and SUVmax.

All patients tolerated the examination well. As the overall SUV mean, median and range of 68Ga-FAPI in primary tumors and metastatic lesions did not differ significantly, researchers analyzed all results in one group.

The highest average SUVmax (SUVmax >12) was found in sarcoma, esophageal, breast, cholangiocarcinoma and lung cancer. The lowest 68Ga-FAPI uptake (average SUVmax

"The remarkably high uptake of 68Ga-FAPI makes it useful for many cancer types, especially in cases where traditional 18F-FDG PET/CT faces limitations," said Uwe Haberkorn, MD, professor of nuclear medicine at the University Hospital of Heidelberg and the German Cancer Research Center in Heidelberg, Germany. "For example, low-grade sarcomas generally have a low uptake of 18F-FDG, causing an overlap between benign and malignant lesions. In breast cancer, 18F-FDG PET/CT is commonly used in recurrence, but not generally recommended for initial staging. And for esophageal cancer, 18F-FDG PET/CT often has only a low to moderate sensitivity for lymph node staging."

In contrast to 18F-FDG PET/CT, 68Ga-FAPI PET/CT can be performed without specific patient preparation such as fasting or recline during uptake time. This is a potential operational advantage for 68Ga-FAPI PET/CT, as it stands to improve patient comfort and accelerate work-flow.

According to Haberkorn, 68Ga-FAPI offers the possibility of a theranostic approach in the future. "Cancer associated fibroblasts have been described as immunosuppressive and as conferring resistance to chemotherapy, which makes them attractive targets for combination therapies," he said. "Because the 68Ga-FAPI tracers contain the universal DOTA-chelator, it is possible to label them with therapeutic radionuclides whose half-life fits to the tumor retention time of the carrier molecule. Since the tracer has been observed to accumulate in several important tumor entities, there may be a huge field of therapeutic application to be evaluated in the future."