Body

PHOENIX - A new study that measured the reliability of administering antibiotics before obtaining blood cultures could end the debate among physicians regarding sepsis management.

Seven emergency departments across North America, including Maricopa Integrated Health System, participated in the research, published Sept. 17 in the Annals of Internal Medicine. The study revealed that initiating antibiotics immediately reduces the sensitivity of blood cultures drawn shortly after treatment. That, in turn, reduces the chances of treating and tailoring antibiotics to specific bacterial and fungal sepsis infections.

"This is a constant debate in the medical field," said Murtaza Akhter, MD, an assistant professor in the Department of Emergency Medicine at the University of Arizona College of Medicine - Phoenix and co-author of the study.

"Emergency medicine physicians want to administer antibiotics as soon as possible because it prevents mortality, whereas internal medicine physicians want two sets of blood cultures before antibiotics are administered so they can more reliably diagnose the organism."

A life-threatening infection that causes the immune system to attack the body, sepsis has a mortality rate of 20 percent. According to the Centers for Disease Control and Prevention, at least 1.7 million adults in the United States develop sepsis each year.

The cornerstone of sepsis management is early administration of an antimicrobial, which kills or inhibits the growth of microorganisms such as bacteria or fungi. However, guidelines recommend two blood cultures be drawn before starting antimicrobial therapy, resulting in significant delays and decreasing the chance of survival.

"It was unknown how quickly blood cultures lose their ability to grow organisms after antibiotic administration," Dr. Akhter said.

"Now we know that even if blood cultures are performed very rapidly after antibiotics, they lose a significant amount of their diagnostic ability."

Dr. Akhter, who also is an attending physician at Maricopa Integrated Health System, said the study tells physicians that blood cultures performed after antibiotics are unreliable.

"Although administering antibiotics to septic patients is important, it is imperative to get at least one blood culture before providing the treatment."

Prior to this study, it was unknown how quickly antibiotic sensitivity changes. Some physicians thought that if you administer antibiotics shortly before blood cultures, you could still properly diagnose the "bug." However, this study revealed that this strategy fails because the cultures are affected rapidly after antibiotic administration.

"We already knew that emergency physicians were correct to not delay antibiotics, but now we know that internal medicine doctors were also correct in that blood cultures after antibiotics are not as reliable," Dr. Akhter said.

Men at high risk of developing breast cancer may benefit from mammography, or breast X-ray, screening for the disease, a new study shows.

The study, publishing in the journal Radiology online Sept. 17, involved 1,869 men, ages 18 to 96, who had a mammogram at NYU Langone between 2005 and 2017. Some sought testing (diagnostic mammogram) because they felt a mass in their breast, while others had no symptoms and wanted to be screened because a family member had recently been diagnosed with the disease.

In total, 41 men were found to have breast cancer, as confirmed by breast tissue biopsy. Among the 271 men who had screening exams, five had the disease. All with breast cancer had surgery (mastectomy) to remove their tumor.

Researchers at NYU School of Medicine and its Perlmutter Cancer Center conducted what they say is the largest review in the United States of the medical records of men who have had a screening mammogram.

A key study finding was that mammography was more effective at detecting cancer in high-risk men than is the norm for women at average risk of breast cancer. For every 1,000 exams in these men, 18 had breast cancer. By contrast, the detection rate for women is roughly five for every 1,000 exams. Researchers attribute this result in part to the lower amount of breast tissue in men. More tissue can mask the detection of small tumors.

"Our findings show the potential of mammography in screening men at high risk for breast cancer and in detecting the disease well before it has spread to other parts of the body," says study lead investigator and Perlmutter diagnostic radiologist Yiming Gao, MD.

Current National Cancer Care Guidelines only recommend checking for breast cancer as part of annual physical exams, not using more sensitive imaging tests like a mammogram, for men age 35 and older with BRCA mutations, says Gao, an assistant professor in the Department of Radiology at NYU Langone Health.

Among the study's other main findings was that men who had already had breast cancer were 84 times more likely to get it again than men who had no personal history of the disease. Men with an immediate relative who had breast cancer, such as a sister or mother, but not a cousin, were three times more likely to develop the disease.

"Men at high risk of breast cancer often seek out testing because a female family member had the disease," says study senior investigator and Perlmutter radiologist Samantha Heller, MD, PhD, an associate professor of radiology at NYU Langone Health. "In general, men need to be more aware of their risk factors for breast cancer and that they, too, can develop the disease."

Most of the men in the analysis sought testing because of concerns about a breast mass. Heller cautions, however, that the lack of targeted screening in those at high risk and the tendency to wait to feel a lump before seeking care may explain why men have a higher risk of dying from breast cancer than women, even though the disease is much more common in women.

Other men with elevated risk of breast cancer included those of Ashkenazi descent, an ethnic group widely known for high rates of some cancers (who were 13 times more likely to get breast cancer than non-Ashkenazi men) and those who had genetic mutations, such as BRCA1 or BRCA2, long linked to increased risk for breast cancer (up to seven times more likely than men with no genetic risk).

Before they would recommend any changes to clinical guidelines, Heller and Gao say more research is needed to determine at what age and how often mammograms should be performed in men at high risk.

"With increasing numbers of women and men seeking genetic counseling for breast cancer, there is a need for advice to both men and women about their actual risk and guidance about the best screening practices to make sure if they do get the disease, that it is detected and treated early," says Gao.

The team plans to expand their analyses to include data from other cancer centers and to better define the risk relationships among family members.

Most of the pups born in an elephant seal colony in California over a span of five decades were produced by a relatively small number of long-lived "supermoms", according to a new study by researchers at the University of California, Santa Cruz.

The long-term study, published September 17 in the Canadian Journal of Zoology, documented the lifetime reproductive success of 7,735 female northern elephant seals at the Año Nuevo rookery north of Santa Cruz. Only 6 percent of the females gave birth to 10 or more pups during their lifetimes, and those "supermoms" accounted for more than half (55%) of the total pup production.

"It's surprising because there are so many more young females than older females, and you expect them to contribute more to the population. But it doesn't work out that way, because most of them don't live very long," said Burney Le Boeuf, professor emeritus of ecology and evolutionary biology at UC Santa Cruz and lead author of the paper.

In fact, the researchers found that three-quarters of the weaned female pups die before reaching maturity and never breed at all. Of the ones that survive to maturity, most only breed one to three times before they die. Breeding takes a toll on the young females, who must invest a lot of energy in their pup at a time when they themselves are still growing, Le Boeuf said.

"The supermoms are able to pull it off," he said. "There aren't many of them, but they have a tremendous influence on the next generation."

The longest-lived female in the study lived to age 23 and produced 17 pups in her lifetime. Another supermom produced pups in 16 consecutive years.

Female elephant seals give birth annually to a single pup in winter. They spend four weeks on the beach nursing their pup, relying entirely on stored reserves, before weaning the pup and heading out to sea to feed. Once a female elephant seal begins breeding at the age of three or four, she is typically either pregnant or nursing for the rest of her life.

During their first trips to sea, the weaned pups are naive and may struggle to find enough food or fall prey to sharks or orcas. Because deaths almost always occur at sea, it is hard to say which are the most important causes of the high mortality rate for young elephant seals.

The surviving females get larger as they age, and bigger moms give birth to bigger pups, which are more likely to survive to maturity and breed. The key to the high productivity of the elephant seal supermoms is simply that they live longer than other females and breed as often as possible, Le Boeuf said.

Lifetime reproductive success is an important measure of evolutionary fitness, a central concept in natural selection. Yet studies of this kind are rare in wild animals because it is so hard to track large numbers of individuals throughout their lifetimes. Researchers have tagged elephant seals at Año Nuevo every year since 1963, not long after the colony was established in 1961. The elephant seal research program at UC Santa Cruz continues to study the colony, and the electronic tagging devices now used to track the seals have grown increasingly sophisticated.

"It's unusual to be able to follow a wild animal throughout its life and determine how successful it is at breeding," Le Boeuf said. "With the elephant seals at Año Nuevo, we've been able to follow them for two generations, more than 50 years, in part because of the proximity of this colony just up the coast from the UCSC campus."

The Año Nuevo Reserve, part of the UC Natural Reserve System, is an important breeding site for many species of marine mammals and birds.

The excessive growth of a baby in the womb, a common complication of gestational diabetes, begins weeks before women are tested for the disease, according to new research being presented at this year's European Association for the Study of Diabetes (EASD) Annual Meeting in Barcelona, Spain (16-20 September).

The analysis of almost 8,000 singleton pregnancies in South Korea revealed that in women subsequently diagnosed with gestational diabetes, abdominal fetal growth was already abnormally large between 20 and 24 weeks--more than 4 weeks before the recommended screening time.

Given the high risk of complications for both mother and baby from maternal diabetes, screening women earlier on in pregnancy is likely to improve their health outcomes, researchers say.

"Abdominal overgrowth of the baby in the womb is believed to indicate fetal obesity, not just a big baby", explains Dr Yoo Lee Kim from CHA University, Republic of Korea who led the research. "Our findings suggest that diagnosing gestational diabetes and implementing interventions to reduce the risk of excessive fetal growth such as diet and exercise earlier in pregnancy may be necessary to prevent harm to mothers and their babies."

Gestational diabetes, a temporary form of diabetes in which hormonal changes disrupt insulin function, affects 3-20% of pregnant women, with those who are obese and/or older at greater risk. Women who develop gestational diabetes are seven times as likely to develop type 2 diabetes in the years following pregnancy. If left undiagnosed and untreated, the condition can also cause the unborn child to have increased birthweight, higher body fat, and lower insulin sensitivity, and increases the likelihood of obesity and diabetes in later life.

Current guidelines in South Korea, the UK, and USA recommend that all pregnant women are screened for gestational diabetes using an oral glucose test at 24-28 weeks of pregnancy. However, previous research suggests that excessive fetal growth can already be detected at the time of screening (24-28 weeks), especially in older women and those with obesity. Whether the onset of this fetal growth disorder predates the recommended screening time is unclear.

To determine whether fetal overgrowth is already present at 20-24 weeks' gestation, researchers analysed medical records of 7,820 pregnant women attending the outpatient clinic of Cha Gangnam Medical Center in Seoul, Korea. Ultrasound scans were used to measure the fetuses' abdominal circumference, head size, and femur length at least 4 weeks before screening for gestational diabetes (at 22 weeks' gestation; 7297 scans), at the same time as the screening test (26 weeks; 5388 scans), and at near term (35 weeks; 5404 scans).

At the 22nd week of pregnancy, ultrasound scans revealed that the fetuses of mothers subsequently diagnosed with gestational diabetes were already significantly larger in abdominal circumference than the babies of women with normal glucose tolerance, and they remained abnormally large through the 35th week of pregnancy. However, head size and femur length were not significantly different between the two groups.

Even among women without diabetes, the babies of mothers who were older or obese were at far greater risk of being abnormally large in abdominal circumference at the 22 week scan, but not in younger and non-obese women.

Dr Kim concludes: "Early screening and careful monitoring may be particularly beneficial for obese and older mothers, as fetal abdominal growth is already abnormal at 5 months in these high-risk women, meaning that their babies are already large at the time of diagnosis."

This is an observational study, so no firm conclusions can be drawn about cause and effect, and the authors point to several limitations including that the study was done in a single centre in South Korea which could affect the generalisability of the results. Additionally, they could not determine exactly why the foetuses of women with gestational diabetes were larger than foetuses in the non-diabetic group.

Meal type and size are the most important factors influencing the accuracy of carb-counting for the control of blood sugar in type 1 diabetes, according to new research being presented at this year's European Association for the Study of Diabetes (EASD) Annual Meeting in Barcelona, Spain (16-20 September).

The results highlight the need for better information to help people with type 1 diabetes improve the accuracy of their carb-counting and reduce the risk of hypoglycemia (low blood glucose levels) that can lead to cognitive decline, cardiovascular events, and even death, researchers say.

People living with type 1 diabetes must manage their daily carbohydrate intake to keep glucose levels in check. Most carbohydrates are converted into glucose and directly affect blood sugar levels. Carbohydrate counting is widely used as a way of matching insulin requirements with the amount of carbs consumed.

However, errors in carb-counting are common and can be critical. Underestimating meal carbohydrate content can raise the amount of sugar in the bloodstream leading to hyperglycemia (high blood sugar), while carbohydrate overestimation can cause hypoglycemia (low blood sugar).

To investigate which factors affect carb-counting errors most, researchers analysed data on 50 adults with type 1 diabetes from a previously published study of carbohydrate counting accuracy [1]. Over 3 days, participants estimated the amount of carbohydrate in their meals. To determine participant's carb-counting error, the carbohydrate content of each meal was also calculated by a dietitian.

Researchers then used modelling to identify which patient- and meal-related factors had an effect on carb-counting error. These included a participant's level of education, duration of insulin treatment, age, body weight, meal's carbohydrate, fat, energy, protein, and fibre content, and type of meal (i.e., breakfast, lunch, dinner, or snack).

They found that carbohydrate content and meal type were the most important factors influencing the accuracy of carb counting. Specifically, participants made more carb-counting errors for larger meals (i.e. lunch and dinner), and smaller errors for smaller meals (i.e. breakfast and snacks).

"Glucose control around meal times remains challenging for people with type 1 diabetes. Our findings underscore the need for better information to help patients better estimate the carbohydrate content of their meals", says author Dr Martina Vettoretti from the University of Padova in Italy, where the research was conducted as part of the ongoing European research project Hypo-RESOLVE.

"Once included in type 1 diabetes computer simulations, our model will enable researchers to assess the impact of carb-counting error on blood sugar control and, more in general, to help study behavioural risk factors for hypoglycemia and assess the potential benefits of addressing them."

In a paper published today in the Journal of Medical Screening, researchers from King's College London and Queen Mary University of London have found that despite free cancer screening programmes, only 35% take part in all offered programmes.

In England, women are invited for screening for three types of cancer concurrently in their sixties; for the last cervical screen before they exit the programme, for breast screening every three years, and for bowel screening every two years. This means that an average woman aged 60 can expect to receive five or six cancer screening invitations by the time she turns 65. In England, cancer screening is provided by the NHS free of charge.

In this study, researchers categorised a sample of just over three thousand eligible women in their sixties according to the last screening round. They looked into women's participation in all three programmes.

Results showed that:

35% took part in all three screening programmes;

37% participated in two programmes;

17% accessed one type of screening; and

10% were not screened at all.

They also found that general practices with a higher proportion of unemployed patients and a higher number of smokers had a lower rate of take-up of all three screening programmes. Conversely, take-up was more frequent among practices in areas of less deprivation, with a higher proportion of women with caring duties, those with long-term health conditions, and those with a high level of patient satisfaction with the practice itself.

"To lower the chances of dying from certain cancers, it is important for the population to attend all offered screening programmes," said lead author Dr Matejka Rebolj from King's College London.

"We know from the official statistics that the majority of women are up to date with breast screening, but this drops to just over 50% when it comes to bowel screening. It is worrying that only a third of women are up to date with all offered cancer screenings and that 10% remained completely unscreened in the last round. Indeed, similar patterns have been reported from other countries too.

"It is crucial for us to look at the take-up rates in certain areas and in certain practices and address women's preferences for future screening programmes. We need to understand and target specifically those women who obtain some screening, but decide not to take up all the life-saving screening that is offered to them by the NHS. It is important that policy makers now look at these findings to inform what can be done in the future to reduce the significant number of deaths in the over 60-year olds."

Senior author Professor Stephen Duffy from Queen Mary University of London said: "These results demonstrate the inequalities in cancer screening participation, with the lowest levels of participation in the areas of highest deprivation.

"Since most women had at least one form of screening, we know that there isn't an objection to screening as a whole. However, individuals find some screening procedures less acceptable than others, so the key to improving participation is making the screening experience better.

"We've seen this work with a new and less burdensome test in bowel cancer screening, which was considerably more acceptable and resulted in a substantial increase in uptake. Most encouragingly, the greatest improvements in uptake were seen in those who previously had the lowest participation levels."

Men with the BRCA2 gene fault have an increased risk of prostate cancer and could benefit from PSA (prostate specific antigen) testing* to help detect the disease earlier, according to researchers funded by Cancer Research UK**.

Previous studies have shown that PSA is not a suitable test for screening for prostate cancer in the general population, and this remains the case. There are limitations to the PSA test - including false positives, false negatives and overdiagnosis***.

But new research found that PSA tests were more likely to pick out more serious forms of prostate cancer in men who carry the BRCA2 gene fault than in non-carriers - suggesting these men could benefit from regular PSA testing.

In the study published today (Tuesday) in European Urology, researchers at The Institute of Cancer Research, London, looked at around 1400 men**** and compared those who don't carry the BRCA2 gene fault with those who do.

Men were offered a yearly PSA test and depending on the result, they were either offered a biopsy to confirm their disease and treated if needed or asked to come back the following year.

The researchers found that men who carry the BRCA2 gene fault were almost twice as likely to be diagnosed with prostate cancer than non-carriers.

They also found that carriers were diagnosed at a younger age - an average of 61 compared with 64 in non-carriers.

Importantly, men with the BRCA2 gene fault were diagnosed with more serious tumours - with 77% of men having clinically significant***** disease compared with 40% of non-carriers.

The study wasn't able to look at whether PSA testing reduced the number of men who died from prostate cancer, which is needed to prove the value of screening in any group.

There are many different things that can raise PSA levels, including an enlarged prostate, certain medications, urinary tract infections or recent ejaculation.

And receiving a false positive result can lead to unnecessary worry and unnecessary biopsies.

This research provides more evidence that the BRCA2 fault increases the risk of prostate cancer in men and shows that a better test is needed to diagnose them.

The BRCA1 and 2 genes are linked to an increased risk in breast and ovarian cancer. But it's less well known that the BRCA2 fault also increases the risk of prostate cancer, although we don't know by exactly how much.

Estimates are around 1 in 300 men could be carrying the gene fault, but only some of them will go on to develop prostate cancer.******

Study leader, Professor Rosalind Eeles, Professor of Oncogenetics at The Institute of Cancer Research, London, and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust, said: "For women who undergo genetic testing, options are available to them if they carry a BRCA fault, including preventative surgery and increased screening. But there's no prevention pathway in place if men decide to find out if they're a carrier. Which is why our research is so important.

"Men may get tested for the BRCA fault due to a family history of breast cancer, as they could pass the gene onto their children, which is especially significant if they have daughters. And our research offers this group of men more insight into their own health.

"Based on our results, we would recommend offering men who carry a fault in the BRCA2 regular PSA tests, so that they can be diagnosed and treated earlier."

Professor Charles Swanton, Cancer Research UK's chief clinician, said: "Understanding more about people at higher risk of prostate cancer is an incredibly important area of research.

"Previous studies have shown that PSA is not a suitable test for screening for prostate cancer in the general population. But we still need to understand whether PSA testing would reduce deaths from the disease in any high-risk groups before we make any recommendation.

"All doctors want the best for their patients and don't want to leave any stone unturned, so some may explain the potential risks associated with PSA testing and still recommend this in high-risk groups despite not knowing that it reduces deaths. Men who are worried about their prostate cancer risk or have a family history should discuss it with their doctor."

Scientists have shown for the first time evidence that early sampling of blood for microorganisms in sepsis is critical to treating the common and potentially fatal condition.

In an international study including researchers from the University of British Columbia (UBC), McGill University and Harvard Medical School, scientists found that in order to better treat sepsis, emergency rooms must strictly follow sepsis guidelines, which demand trained personnel and proper equipment.

"It's crucial for emergency room clinicians to quickly diagnose and treat sepsis patients within the hour, if possible, to prevent further organ damage and possible death," said Dr. David Sweet, senior study author, clinical associate professor of emergency medicine in the faculty of medicine at UBC, and a critical care physician at Vancouver General Hospital.

Sepsis, a condition caused by the immune system's response to infection, triggers a series of reactions including swelling, blood-clotting and organ damage. It was the 12th leading cause of death in Canada in 2011 (the latest year of comparable data) and disproportionately affects seniors, cancer patients, diabetics and others.

The five-year study (2013-2018) published today in the Annals of Internal Medicine involved 325 patients in seven hospitals (including Vancouver General, St. Paul's, Lions Gate and Surrey Memorial) who arrived at the hospital complaining of sepsis-like symptoms such as increased heart rate, painful urination and confusion.

According to international sepsis guidelines, if health-care workers suspect a patient is suffering from sepsis, they should order a blood test before--not after--administering antibiotics. If the patient receives antibiotics (typically via intravenous therapy) before the blood test, the telltale bacteria may not be detected and the cause of sepsis will remain undiagnosed.

The study found that post-antibiotic blood tests were 50 per cent less likely to identify the cause of sepsis in patients compared to blood tests taken before antibiotic treatment.

"Our study has, for the first time ever, produced clear evidence supporting current sepsis guidelines and underscores the urgent need for proper sepsis protocols," Sweet said.

If patients are properly diagnosed, antibiotics are prescribed more efficiently, which reduces resistance in patients and the probability of additional infections--all at less cost to the health-care system.

"Emergency rooms must place more emphasis on sepsis guidelines and make sure they have the resources to implement them, for the sake of patients and our health-care system," Sweet said.

A new needle-free flu vaccine patch revved up the immune system much like a traditional flu shot without any negative side effects, according to a study published in the Journal of Investigative Dermatology. Though the research is in the early stages (the patch hasn't been tested in humans), it's an important step toward a technology that could replace needle-based vaccination methods that require administration by health care workers and biohazard waste removal.

"Scientists have been studying needle-free vaccine approaches for nearly two decades, but none of the technologies have lived up to the hype," said Benjamin L. Miller, Ph.D., corresponding author and Dean's Professor of Dermatology at the University of Rochester Medical Center. "Our patch overcomes a lot of the challenges faced by microneedle patches for vaccine delivery, the main method that's been tested over the years, and our efficacy and lack of toxicity make me excited about the prospect of a product that could have huge implications for global health."

Common skin disease paves the way for needleless flu shot

Transporting big molecules like flu vaccine proteins across the skin is difficult to do, as the skin is intended to keep things out of the body, not to let them in. The study team took lessons learned from the research and treatment of a common inflammatory skin disease to overcome this hurdle and inform their flu vaccine patch strategy.

In patients with eczema, or atopic dermatitis, the skin barrier is leaky, allowing pollens, molds and a host of other allergens to enter through the skin and be sensed by the immune system. Lisa A. Beck, M.D., corresponding author and Dean's Professor of Dermatology at the University of Rochester Medical Center discovered that the expression of a protein called claudin-1 helps maintain barrier strength and lessen the permeability of the skin. Claudin-1 is significantly reduced in eczema patients (hence the leaky skin barrier) compared to individuals without the disease.

In past research, Beck found that decreasing claudin-1 expression in skin cells from healthy donors made the skin more permeable. Beck, Miller, and first author Matthew Brewer, Ph.D., wondered if they could use this induced permeability to get a flu vaccine virus through the skin. The key would be to disrupt the skin barrier long enough to deliver the virus, but not so long to let unwanted things in.

How it works: Dermatology, chemistry and vaccine biology collide

Miller, a chemist, worked with Brewer, who was trained in vaccine biology and immunology, to develop synthetic peptides that bind to and inhibit claudin-1 in an effort to open up the skin barrier. They tested their formulations in human skin cells and identified a peptide that disrupted the barrier without any toxic effects.

Next, they designed a patch containing the synthetic peptide and a recombinant flu vaccine and tested two scenarios. In the first, they placed the patch on mice to prime the immune system and subsequently administrated an intramuscular flu shot to boost immunity. In the second they did the opposite, delivering an intramuscular flu shot first to prime the immune system followed by the patch to boost immunity.

In both scenarios they placed the flu vaccine patch, which looks like a tiny piece of tape, on the backs of mice and left if there for as little as 18 and as long as 36 hours. The patch effectively opened up the skin barrier, as measured by water loss through the skin.

When the patch was placed first there wasn't a significant immune response, suggesting that it might not be effective at taking a flu naïve infant who hasn't received a flu shot or been exposed to the virus to adequate protection. But, it did initiate a robust immune response (as measured by an increase in antibodies to the flu vaccine virus) when it followed the intramuscular shot, suggesting it could boost preexisting immunity for anyone six months or older who has been vaccinated and/or exposed to the virus (mimicking what happens when we get seasonal flu shots year after year).

Importantly, the team saw no physical changes in the skin over the three month period the mice were observed, meaning that the brief barrier disruption didn't increase the risk of infection.

"When we applied the patch with the peptide the mouse skin became permeable for a short time," said Brewer, a postdoctoral fellow in both the Beck and Miller labs. "But as soon as the patch was removed the skin barrier started to close. We saw significant differences as early as one hour after removal, and by 24 hours the skin was back to normal, which is great news from a safety standpoint."

Improved vaccine delivery for global health

Current needle-based vaccines are effective but require medical personnel to deliver, generate biohazards (sharps) requiring disposal, and cause patients pain and anxiety - all barriers to delivery in developing world countries, which are the areas of greatest need.

"These countries don't have the manpower to vaccinate entire populations," said Beck. "On top of that, there's an aversion to health care in many of these communities. A needle is painful, it's invasive, and that makes things more difficult when you are dealing with a cultural bias against preventative medicine."

A flu vaccine patch could provide a non-invasive way to administer vaccines quickly and cheaply to large numbers of people.

"If you want to vaccinate a village in Africa you don't want to do it with needles," added Miller. "A patch doesn't have to be refrigerated, it can be applied by anyone, and there are no concerns about disposal or needles getting reused."

What's next?

There's a lot more work to be done on the flu vaccine patch, including additional animal studies to help the team optimize the amount of time the patch must remain on the skin to appropriately boost the immune response. The team hopes to conduct human trials in the future, and believes that if the patch is effective in people it could work for diseases for which there's already a needle-based vaccine.

Initial results of NRG Oncology Clinical Trial RTOG 9601 in men with biochemically recurrent prostate cancer receiving salvage radiotherapy (SRT) demonstrated improvement in OS from the addition of long-term hormone therapy to SRT. However, a secondary analysis indicates that all patients do not benefit and the addition of long-term anti-androgen therapy did not improve overall survival (OS) rates and could increase other-cause mortality (OCM) for some patients depending on pre-treatment PSA level. Data now shows that pre-SRT prostate-specific antigen (PSA) was a prognostic and predictive biomarker in determining the benefit of the addition of anti-androgen therapy to early SRT. These results were presented during the plenary session of the American Society of Radiation Oncology's (ASTRO) Annual Meeting in September 2019. The abstract is one of four abstracts chosen from over 3,000 submitted abstracts for the plenary session.

NRG-RTOG 9601 was a randomized clinical trial that compared SRT followed by two years of anti-androgen treatment or a placebo in men with biochemically recurrent prostate cancer. Trial participants were randomly assigned to one of the two treatment arms. Results of the initial trial demonstrated improvement in OS from the addition of long-term hormone therapy to SRT at a median follow-up of 13 years. However, the patient population enrolled on this trial was representative of patients in the late 1990s, but patients today are usually treated at much lower PSAs closer to the time of biochemical recurrence. Given the known side effects of hormone therapy, including worsening of cardiac disease, the question becomes in a more representative population of patients receiving early salvage RT at lower PSAs would there still be net benefit. Thus, a secondary analysis of NRG-RTOG 9601 was designed to address if pre-SRT PSA could serve as a prognostic and predictive biomarker of benefit from hormone therapy.

Patients on NRG-RTOG 9601 were stratified by entry PSA (0.2-1.5 vs >1.5-4.0 ng/mL) and randomly assigned to receive either nonsteroidal anti-androgen therapy (bicalutamide) or placebo for two years. 760 patients were evaluable following treatment and 85% percent of those patients were in the pre-SRT PSA of ?1.5 ng/mL stratum. There was no statistically significant overall survival benefit for men with PSAs ?1.5 ng/mL (HR 0.87 [95%CI 0.66-1.16]).Furthermore, men with PSAs 1.5 ng/mL (HR 0.45 [0.25-0.81]).

"Further research is needed to determine which patients receiving early SRT will benefit from hormone therapy. The currently enrolling NRG Oncology clinical trial NRG-GU006 is designed to address this question by measuring the biochemical progression-free survival rates men with post-prostatectomy PSA recurrences who previously received SRT. Men on this trial will either receive SRT alone or a combination of SRT followed by next-generation anti-androgen therapy," stated Daniel Spratt, MD, of the University of Michigan and the lead author of the secondary analysis of NRG-RTOG 9601 and co-principal investigator of NRG-GU006.

WASHINGTON (Sept. 16, 2019) -- Automated external defibrillators (AEDs) are often placed in areas of low risk and may be unavailable during certain times of the day. Determining the optimal location for AEDs may lead to increased defibrillation by bystanders and increased survival in those experiencing out-of-hospital cardiac arrest (OHCA), according to research published today in the Journal of the American College of Cardiology.

The use of publicly accessible AEDs is associated with significantly better outcomes in patients experiencing OHCA as long as they are available during a time of need.

Study researchers used computer models to determine the optimal location of AEDs in Copenhagen. This in silico--or computer simulated--trial mimicked a randomized clinical trial. This study design is quick and cost-effective while also allowing for researchers to conduct a study for longer periods of time and to incorporate a control that might not otherwise be possible. This is the first in silico trial to examine AED intervention.

Using historical data, they were able to determine locations where OHCAs were more likely to occur and compared them against real AED deployments. OHCAs occurring from January 1994 - September 2007 were used to train the models and OHCAs from the study period of October 2007 - December 2016 were analyzed. The study only included OHCAs that occurred in public locations.

"Our trial design ensured that the optimization methods were not advantaged compared to the real AED placements," said study author Timothy C.Y. Chan, PhD, Canada Research Chair in Novel Optimization and Analytics in Health and the director of the Centre for Healthcare Engineering at the University of Toronto. "The optimization models placed the same number of AEDs every month that were placed in reality."

The researchers implemented two AED placement policies as interventions. Intervention No. 1 placed AEDs in buildings based on location and hours of operation, while intervention No. 2 placed AEDs outside based on location and assuming 24/7 accessibility. The control group included all real AED placements in Copenhagen during the study period. The primary outcome was the total number of OHCAs that occurred within a 100m straight-line, equal to a 150m pedestrian route, from an available AED.

While the actual AEDs covered 22 percent of all OHCAs during the study, those from intervention No. 1 and No. 2 would have covered 33.4 percent and 43.1 percent, respectively. These increases amounted to relative coverage gains of 52 percent and 95.9 percent, respectively.

"Our findings show that if we could go back in time to the historical inception of the AED program in Copenhagen and place AEDs in accordance with our best optimization model, we would have achieved nearly double the OHCA coverage that was achieved in reality in the subsequent nine years," Chan said. "Our inclusion of two optimization approaches highlights the potential benefits of improving AED accessibility and placement, as well as having AED networks designed by a central decision maker."

The researchers also determined that bystander defibrillation increased significantly from 14.7 percent in the control group to 22.5 percent for intervention No. 1 and 26.9 percent for intervention No. 2. Predicted 30-day survival increased from 31.3 percent in the control group to 34.7 percent for intervention No. 1 and 35.4 percent for intervention No. 2.

These study results are consistent with previous studies that have shown a positive correlation between distance to an AED and the outcomes of bystander defibrillation and survival.

The optimization models in this study were originally developed for use in Toronto, a city with different OHCA incidence, city structure and population characteristics compared to Copenhagen. According to the authors, these findings therefore provide further validation for the generalizability of optimization models for AED placement.

The authors acknowledge that while these results are promising, they suggest the need for clinical trials to verify the estimated impact on clinical outcomes. Additionally, AED placement is only one factor in improving OHCA survival. Public education campaigns are needed to improve bystander awareness and a willingness to act, while drone delivery of AEDs and smartphone apps may also increase bystander CPR and AED utilization.

Mosquitoes are more likely to acquire the dengue virus when they feed on blood with low levels of iron, researchers report in the 16 September issue of Nature Microbiology. Supplementing people's diets with iron in places where both iron deficiency anemia and dengue fever are a problem could potentially limit transmission of the disease, but there are risks.

Dengue fever is a disease spread by mosquitoes in the tropics, primarily Central America and northern South America, the Caribbean, sub-Saharan Africa and southeast Asia. It has also been transmitted in the southeastern US. Dengue causes a fever, rash, and terrible aches, and can also lead to shock and death. It causes about 60 million cases a year, with 18% requiring hospitalization and about 13,600 deaths, and costs about $9 billion annually worldwide.

Dengue is most commonly acquired in urban environments, and the expansion of cities in the tropics has been accompanied by an expansion in dengue infections. A vaccine exists, but it can actually make the disease worse if given to someone who has never been previously infected. Public health officials are actively looking for ways to reduce the prevalence of the disease.

UConn Health immunologist Penghua Wang wanted to see if blood quality had an impact on the spread of dengue virus. Blood levels of various substances can vary tremendously from person to person, even among healthy people. Wang and colleagues at Tsinghua University and State Key Laboratory of Infectious Disease Prevention and Control in Beijing, King Mongkut's Institute of Technology Ladkrabang in Bangkok, and the 920 Hospital Joint Logistics Support Force in Kunming ran a series of experiments to explore the idea.

They collected fresh blood from healthy human volunteers, then added dengue virus to each sample. Then they fed the blood to mosquitoes, and checked how many mosquitoes were infected from each batch. They found it varied quite a lot. And the variation correlated very closely with the level of iron in the blood.

"The more iron in the blood, the fewer mosquitoes were infected," says Wang. The team found it held true in a mouse model, too: mosquitoes feeding on mice infected with dengue were much more likely to acquire the virus if the mice were anemic.

The reason has to do with the mosquitoes' own immune systems. Cells in a mosquito's gut take up iron in the blood and use it to produce reactive oxygen. The reactive oxygen kills the dengue virus.

"In areas where dengue is endemic, iron deficiency is more common. It doesn't necessarily explain it, the high prevalence of dengue...but it could be possible that iron supplementation could reduce dengue transmission to mosquitoes in those areas," Wang says. But there's a big caveat.

Malaria tends to be common in the same areas as dengue. And plasmodium, the microorganism that causes malaria, thrives in an iron rich environment and might actually worsen if everyone is supplementing with iron. Public health authorities need to weigh the costs and benefits before embarking on any population-wide supplementation program.

In any case, Wang says, understanding how dengue is transmitted will help public health authorities and scientists develop new ways to control the disease, and hopefully similar viruses such as Zika and West Nile virus as well.

More than 70% of U.S. adults are unaware that human papillomavirus (HPV) causes anal, penile, and oral cancers, according to an analysis led by researchers at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health and published in the current issue of JAMA Pediatrics.

Men are also less likely than women to know that the virus carries a risk of cancer, said Ashish A. Deshmukh, PhD, MPH, assistant professor at UTHealth School of Public Health, who led the study that included 2,564 men and 3,697 women who took part in the Health Information National Trend Survey. Two-thirds of men and one-third of women ages 18-26 did not know that HPV causes cervical cancer. More than 80% of men and 75% of women in the same age group - and 70% of all American adults of any age - did not know that HPV can cause oral, anal, and penile cancers.

Human papillomavirus is the most common sexually transmitted infection. There are many types of HPV, but some are more likely to cause cancers and genital warts. The HPV vaccine can protect against cancers caused by the virus.

The analysis by Deshmukh and colleagues also showed that, of people who were vaccine-eligible or had vaccine-eligible family members, only 19% of men and 31.5% of women received recommendations for the vaccine from a health care provider.

According to the U.S. Centers for Disease Control and Prevention (CDC), boys and girls ages 9-14 should receive the two-dose immunization. A three-dose schedule is recommended if the first dose was given on or after the 15th birthday. Recently, CDC also recommended that adults ages 27-45 may decide to get the HPV vaccine based on discussion with their clinician. A 2018 report by the CDC suggested only 51% of those in the recommended age groups were vaccinated.

"The lack of knowledge may have contributed to low HPV vaccination rates in the United States," said Deshmukh.

"Low levels of HPV knowledge in these older age groups is particularly concerning, given that these individuals are (or will likely be) parents responsible for making HPV vaccination decisions for their children," said Kalyani Sonawane, PhD, assistant professor at UTHealth School of Public Health, the study's co-lead author.

"HPV vaccination campaigns have focused heavily on cervical cancer prevention in women. Our findings demonstrate a need to educate both sexes regarding HPV and HPV vaccination," Deshmukh said. "Rates of cervical cancer have declined in the last 15 to 20 years because of screening. On the other hand, there was a greater than 200% increase in oropharyngeal cancer rates in men and a nearly 150% rise in anal cancer rates in women."

Improving HPV vaccination rates is important to reverse rising rates of these cancers, Deshmukh added.

Heart attack is a leading cause of death worldwide and new treatment strategies are highly sought-after. Unfortunately lasting damage to the heart muscle is not uncommon following such an event.

Published in Redox Biology, the pre-clinical study sheds new light on the potential of the acute therapy with α-TOH (vitamin E) in patients presenting with heart attack, and may ultimately offer an effective low-cost treatment.

"One of the most effective anti-oxidant and anti-inflammatory agents is vitamin E and its derivatives," said Professor Karlheinz Peter, the Baker Institute's Deputy Director, Basic and Translational Science and lead author of the study.

"Our treatment regime reflects clinical conditions, where patients could receive their first application of vitamin E in the ambulance or upon their arrival in the emergency department, before reopening and stenting the blocked vessel and the following days in hospital before discharge."

Our next step is to test an already approved formulation of Vitamin E in patients admitted with a heart attack," said Professor Peter. "We plan to prove that heart function is preserved using sensitive magnetic resonance imaging. Thereby, we hope to establish an inexpensive and effective therapy for patients with heart attack."

Nutritional scientist and vitamin specialist from Jena University in Germany, Dr Maria Wallert said interestingly, Vitamin E has been trialled unsuccessfully for preventing heart attacks but has not been investigated for actually treating heart attacks.

"As there is currently no drug available that can reduce the cardiac damage caused by an overshooting inflammation after reopening of a blocked coronary artery, the potential impact of our finding on cardiovascular health would be signi?cant," said Dr Wallert.

The doses of vitamin E given in our study is approved to be safe by the European Commission Scientific Committee on Food. We hereby provide an experimental design which potentially can be translated to human trials without concern surrounding the safety of vitamin E applications.

In a follow-up study conducted in South Africa, Johns Hopkins Medicine researchers say they have evidence that hospital emergency departments (EDs) worldwide may be key strategic settings for curbing the spread of HIV infections in hard-to-reach populations if the EDs jump-start treatment and case management as well as diagnosis of the disease. A report on the findings was published in August in EClinicalMedicine.

"In South Africa and in many other areas of the world, one of the major reasons HIV is spreading is because young men in particular are not virally suppressed, not taking their medication or are unaware of their diagnosis," says Bhakti Hansoti, M.B.Ch.B., Ph.D. M.P.H., , associate professor of emergency medicine at the Johns Hopkins University School of Medicine and lead author of the research paper. She adds that young men are more likely to go to an ED for trauma or violence-related injuries than other clinical settings, and may not have a primary health care provider -- making the ED the only point of entry for health care in general.

Building on a 2018 study of ED patients in South Africa that found that HIV testing in emergency departments is an effective way to identify and diagnose otherwise hard-to-reach people with HIV, the Johns Hopkins Medicine investigators worked with colleagues in three hospital EDs in East London, Mthatha and Port Elizabeth in the Eastern Cape province of South Africa, the country with the world's largest number of recorded HIV infections.

Nearly 38 million people around the world are currently living with HIV, according to the Joint United Nations Programme on HIV/AIDS (UNAIDS). About 20% of people who have HIV live in South Africa. To end the HIV/AIDS epidemic, UNAIDS established treatment targets for 90% of all people with HIV around the world to know their HIV status by 2020, for 90% of those diagnosed to be on HIV treatment known as antiretroviral therapy (ART), and for 90% of all people receiving ART to have undetectable HIV levels in their blood and, therefore, be unable to transmit the virus to others.

"We already know that HIV testing in the ED is critical to achieving these targets, but testing alone is just not going to cut it," says Hansoti. "Testing alone will help us reach that first 90% goal, but to get to the second and third 90%, we believe EDs need to play an active role in treatment initiation." EDs also must initiate follow-up case management and link patients to care outside of the ED, the researchers say.

For the new study, conducted between June 2017 and July 2018, the researchers tested 2,901 male and female patients between the ages of 18 and 70 for HIV in the three EDs. More than 800 (28%) tested HIV positive, of whom 234 (28.9%) were newly diagnosed. The prevalence of HIV in the ED-tested population was significantly higher in women (35.3%) compared to men (20.7%) -- with women ages 36-45 having the highest prevalence (almost 65%) compared with other age groups.

Of all the HIV patients tested for ART, only 54% tested positive for the presence of ART, and 49% of those on ART were found to be virally suppressed. This is significantly below the 90-90-90 targets. While women were more likely to have HIV, the researchers found that men were twice as likely to be unaware of their HIV status and, therefore, also less likely to be on ART and virally suppressed -- and therefore more infectious to their sex partners. The researchers consider young men, in particular, to be "drivers of the HIV epidemic" in South Africa.

The researchers say their findings suggest that EDs around the world should not only implement routine HIV testing to find often-missed patients but also train physicians and nurses to start patients on ART and provide post-test counselling.

"Patients can be tested for HIV while waiting in the emergency department and then, if positive, be counseled and offered treatment or, at the least, followed up in a specialized HIV care facility," Hansoti says.

The research team noted the challenges in implementing HIV care services in the ED, including the high volume of patients, and provider hesitation to start patients on ART due to possible comorbidities and liabilities.

Still, the researchers believe these initiatives are needed to curb the HIV epidemic. "Our research shows there are many patients with HIV in the emergency department who are untreated, undertreated and undiagnosed," Hansoti says.

The researchers say they also plan to explore HIV care strategies best suited to the ED.