Body

What The Study Did: Weekly changes in U.S. deaths from March 1 through May 30, 2020, due to any cause and deaths due to pneumonia, influenza or COVID-19 are investigated in this observational study.

Authors: Daniel M. Weinberger, Ph.D., of the Yale School of Public Health in New Haven, Connecticut, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamainternmed.2020.3391)

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

Major weaknesses exist in the evidence base for covid-19 antibody tests, finds a review of the latest research published by The BMJ today.

The evidence is particularly weak for point-of-care tests (performed directly with a patient, outside of a laboratory) and does not support their continued use, say the researchers.

Serological tests to detect antibodies against covid-19 could improve diagnosis and be useful tools for monitoring levels of infection in a population. The UK Prime Minister Boris Johnson has described antibody tests as "game-changing" in its response to the pandemic, but it is important to formally evaluate whether there is sufficient evidence that they are accurate.

So an international team of researchers set out to determine the diagnostic accuracy of antibody tests for covid-19.

They searched medical databases and preprint servers from 1 January to 30 April 2020 for studies measuring sensitivity and/or specificity of a covid-19 antibody test compared with a control test.

Sensitivity measures the percentage of people who are correctly identified as having a disease, while specificity measures the percentage of people who are correctly identified as not having a disease.

Of 40 eligible studies, most (70%) were from China and the rest were from the UK, US, Denmark, Spain, Sweden, Japan and Germany.

Half of the studies were not peer reviewed and most were found to have a high or unclear risk of bias (problems in study design that can influence results). Only four studies included outpatients and only two evaluated tests at the point of care.

When sensitivity results for each study were pooled together, they ranged from 66% to 97.8% depending on the type of test method used, meaning that between 2.2% and 34% of patients with covid-19 would be missed.

Pooled specificities ranged from 96.6% to 99.7%, depending on the test method used, meaning that between 3.4% and 0.3% of patients would be wrongly identified as having covid-19.

Pooled sensitivities were consistently lower for the lateral flow immunoassay (LFIA) test compared with other test methods. The LFIA test is the potential point-of-care method that is being considered for 'immunity passports.'

Based on these results, the authors explain that, if an LFIA test is applied to a population with a covid-19 prevalence of 10%, for every 1000 people tested, 31 who never had covid-19 will be incorrectly told they are immune, and 34 people who had covid-19 will be incorrectly told that they were never infected.

Pooled sensitivities were also lower with commercial test kits (65%) compared with non-commercial kits (88.2%) and in the first and second week after symptom onset compared with after the second week.

The researchers point to some limitations, such as differences in study populations and the potential for missing studies. However, strengths include thorough search strategies and assessment of bias.

"These observations indicate important weaknesses in the evidence on covid-19 serological tests, particularly those being marketed as point-of-care tests," they write.

"While the scientific community should be lauded for the pace at which novel serological tests have been developed, this review underscores the need for high quality clinical studies to evaluate these tools," they conclude. "With international collaboration, such studies could be rapidly conducted."

Residents in all 25 of the U.S. counties hardest hit by COVID-19 began to limit their public movements six to 29 days before states implemented stay-at-home orders, according to Johns Hopkins University researchers.

The decline in the number of daily trips people made as tracked by mobile phone data helped slow the spread of the virus, according to findings published today in The Lancet Infectious Diseases journal from the Johns Hopkins team that created the world-famous online coronavirus tracking map.

"Our results strongly support the conclusion that social distancing played a crucial role in the reduction of case growth rates in multiple U.S. counties during March and April, and is therefore an effective mitigation policy for COVID-19 in the United States," said Lauren Gardner, co-director of the Center for Systems Science and Engineering at Johns Hopkins, who led the research team.

"Critically, if individual-level actions were not taken and social distancing behavior was delayed until the state-level directives were implemented, COVID-19 would have been able to circulate unmitigated for additional weeks in some locations, inevitably resulting in more infections and deaths," Gardner added. "This demonstrates that it is within the power of each U.S. resident to help slow the spread of COVID-19."

Despite some county-level restrictions being implemented earlier than state policies, 21 out of the 25 counties recorded initial declines in movement before even those local steps.

Determining the effectiveness of social distancing is difficult because counties and states implemented different policies at different times. To establish a reliable indicator of social distancing the researchers used real-world mobile phone movement data.

Their first step was to establish a baseline of normal movement between Jan. 8-31. They then examined changes through April 16 in the 25 U.S. counties with the highest numbers of confirmed COVID-19 cases.

From Jan. 24 to April 17, people made far fewer daily trips than they did during the baseline period. Individuals began to reduce movement in early March, indicating that social distancing began well before the first state, California, imposed a stay-at-home directive on March 21.

In New York City, for example, residents had limited movement to 35% of the baseline, the most-significant reduction in movement among the 25 jurisdictions.

Harris County, Texas, which includes Houston, displayed the least change. Its residents slowed their normal movements but only to 65% of the movements measured in January. Data for all 25 counties are detailed in the research.

Social distancing will remain one of the most important ways to control the spread of infections until a vaccine is available.

"Individuals seem to have anticipated public health directives in March and April, despite a mixed political message," Hamada Badr, a co-author and research scientist in the Department of Earth and Planetary Sciences at Johns Hopkins. "As stay-at-home policies began to relax, we urge individuals and governments to make safe and data-driven decisions, to respond to the potential risk of increased infections. More timely, consistent and decisive policy implementation of social distancing and other known effective mitigation measures is urgently needed."

Inhibit the specific activity of a protein affected by a mutation using high doses of a drug is the usual treatment for many cancers. Despite in the first instance this strategy is effective, leads to treatment resistance development by tumor cells through the appearance of secondary mutations, which enhance alternative growth pathways, and allow cells to avoid the effect of the drug. This is the case of non-small cell lung cancer (NSCLC), caused by mutations in the EGFR receptor, in which treatment with EGFR inhibitors leads to resistance.

The study led by Dr. René Bernards of the Netherlands Cancer Institute (NKI), in collaboration with researchers Alberto Villanueva and Ernest Nadal of the Bellvitge Biomedical Research Institute (IDIBELL) and the Catalan Institute of Oncology (ICO), and Agustí Vidal of the Bellvitge University Hospital (HUB), has developed a new therapeutic approach to treat this type of tumor witrh a cocktail of low-dose drugs, called MLD (Multiple Low Dose). This combination seeks to inhibit simultaneously the action of several proteins of the same signaling pathway essential for the tumor cell.

Specifically, in this study published in the Nature Communications journal, they show that at least 20% of the effective dose of the drugs is sufficient to completely block the signaling pathway and cell proliferation when we use a combination of four inhibitors. In vitro studies with cell lines, as well as animal models generated by patient biopsies implantation into mouse lungs, showed a long-lasting response to MLD therapy with no toxic effects associated. Although each drug in low doses had no effect independently, the combination of the four drugs became a synergistic effect that was able to stop tumor growth.

The results of this study show that the combination of several drugs that act on different components of a necessary communication pathway of tumor cells, and also, do it in low doses, entails a longer-term efficacy of antitumor treatments, and avoids the appearance of resistance. Although now it has only been tested in one type of lung tumor, the researchers believe that this new approach could be extensible to other types of tumors. Clinical trials are planned to verify the efficacy of this strategy in patients with NSCLC tumors with EGFR mutation.

LA JOLLA--(July 1, 2020) Chronic liver disease represents a major global public health problem affecting an estimated 844 million people, according to the World Health Organization. It is among the top causes of mortality in Australia, the UK and the United States. At the same time, it is both difficult to manage and there is no FDA-approved anti-fibrotic liver therapy. The microbiome--a complex collection of microbes that inhabit the gut--may be an unexpected indictor of health. Now, a collaborative team of Salk Institute and UC San Diego scientists have created a novel microbiome-based diagnostic tool that, with the accuracy of the best physicians, quickly and inexpensively identifies liver fibrosis and cirrhosis over 90 percent of the time in human patients.

The non-invasive method relies on an algorithm to analyze patient stool samples--which contains traces of what lives in the gut--and could lead to improved patient care and treatment outcomes for liver disease, as detailed online on June 30, 2020 in Cell Metabolism.

"The microbiome is a dynamic living sensor of small changes in health and disease in the body, and as such, it provides an accurate readout of body health," says Salk Professor Ronald Evans, co-corresponding author and holder of the March of Dimes Chair. "Because this diagnostic is fast and low-cost, it could be something that becomes widely used, especially in the many areas that lack specialty clinics and physicians. Simply said, it could be a real game changer, with world-wide implications."

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease globally and can progress to liver fibrosis and cirrhosis and potentially cancer, as the liver starts to experience scarring and cell death. But diagnostic tools for liver fibrosis and cirrhosis are lacking. Biopsies are invasive and can miss injured regions of the liver, and MRIs are expensive and are often not available in rural areas. To address these challenges, the research team explored the microbiome as a way to meet the urgent need for a new test to identify patients at risk.

"We sought to develop a universal, non-invasive test for liver fibrosis and cirrhosis based on a 'microbiome signature' of the disease," says Michael Downes, a Salk senior staff scientist and co-author of the study.

In collaboration with scientists from the UC San Diego Department of Medicine, the team optimized a computational method called machine learning to uncover a complex disease signature based on 19 bacterial species present in the stool samples of a patient group. The signature is made up of the different quantities of bacteria, creating a universal fingerprint for identifying liver fibrosis and cirrhosis. The study included 163 clinical samples from both healthy as well as sick family members to identify variables that were indicative of liver disease.

Using data from microbiome genetic profiling and from metabolites from the stool samples, the researchers discovered a microbiome signature that was associated with a cirrhosis diagnosis with 94 percent accuracy. The microbiome signature could also determine the stage of liver fibrosis, which could allow doctors to grade patients based on their stage of the disease and improve treatment strategies.

"These findings demonstrate that it is possible to use machine learning to identify a universal signature that can be used for accurate diagnosis of a disease, such as liver cirrhosis," says Tae Gyu Oh, first author of the paper and a postdoctoral researcher in the Evans lab. "The patterns we found reflect the complexity of the microbiome and how gut health likely affects disease."

The researchers then applied their microbiome signature to two independent populations of patients from China and Italy. The team's signature could accurately identify cirrhosis in over 90 percent of patients, which validates the power and accuracy of the algorithm across different genetics and diets.

"It is remarkable that a gut microbiome signature derived from patients residing in Southern California for cirrhosis was able to predict cirrhosis in two independent cohorts residing in China and Italy. It speaks to the new discoveries that are yet to be realized in the role of the gut microbiome to diagnose and risk-stratify liver disease," says Rohit Loomba, co-corresponding author and director of the NAFLD Research Center at the UC San Diego School of Medicine. "I think the power of using the microbiome as a diagnostic tool is only starting to be realized."

In the future, the scientists will examine the causal link between the microbiome and liver disease by testing whether restoring parts of the microbiome leads to regression of the disease or removing certain bacteria makes it worse. The team also hopes this approach can be used to characterize additional diseases, such as inflammatory bowel disease, colon cancer, Alzheimer's and other diseases shown to be likely affected by a dysregulated microbiome.

Sophia Antipolis - 1 July 2020: East Germany has many more hospitalisations for heart failure compared to West Germany despite a nationwide healthcare system, according to research presented today on HFA Discoveries, a scientific platform of the European Society of Cardiology (ESC).1

Heart failure is the most common reason for hospital admissions and is responsible for a large part of the total health expenditure on cardiovascular diseases throughout the Western World. A previous study reported that the absolute number of heart failure-related hospitalisations increased by 65% in Germany between 2000 and 2013.2

"Before reunification in 1990, East and West Germany not only had very different social and economic systems but also had distinct healthcare systems," said study author Professor Marcus Dörr of University Medicine Greifswald, Germany.

"In East Germany, the system was nearly completely run by the state (e.g. less than 1% of physicians worked in private practice) and there was a substantial shortage of technical equipment (e.g. one ultrasound device per 32,000 inhabitants in East Germany compared to one per 2,500 in West Germany)," continued Professor Dörr. "Since 1990, both regions have the same federal healthcare system with more physicians in private practice and similar clinical care pathways."

This study analysed whether the change to a shared system affected the number and duration of hospitalisations and in-hospital mortality due to heart failure in West and East Germany from 2000 to 2017. The researchers also examined whether the previously described rise in heart failure-related hospitalisations2 continued and occurred equally in both parts of Germany. Data were obtained from Federal Health Monitoring, an annual census of routine inpatient data.3

The researchers found that the absolute number of hospitalisations due to heart failure continued to increase dramatically across Germany and there were substantial differences between regions.

In 2000 to 2017, the absolute number of hospital admissions due to heart failure throughout Germany increased continuously by 93.9% (from 239,694 to 464,724 cases). This increase was much stronger in East than in West Germany (+118.5% vs. +88.3%) and was higher in each of the federal states in East Germany than in every single state in West Germany.

During the same period, there was only a slight increase in the number of hospitalisations for other diagnoses all over Germany. Heart failure was the leading cause of disease-related hospitalisation in Germany in 2017, again with clear differences between East and West Germany (increase from 1.5% to 2.9% in East vs. 1.4 % to 2.2 % in West Germany).

While the overall length of hospital stays decreased continuously over time, the total number of heart failure-related hospital days increased by 50.6% in East and by 34.6% in West Germany.

In 2017, heart failure remained by far the leading cause of in-hospital death in Germany, accounting for 8.2% of deaths. Again, there were substantially higher rates of in-hospital deaths in East Germany (64 and 65 deaths per 100,000 inhabitants in 2000 and 2017, respectively; an increase of 1.6%) as compared to West Germany (39 and 43 deaths per 100,000 inhabitants in 2000 and 2017, respectively; an increase of 10.3%).

Professor Dörr said: "As East and West Germany started with different healthcare systems, we hypothesised that heart failure hospitalisation patterns would align after reunification. This hypothesis had to be rejected and, in fact, the opposite was found."

He noted that the observed differences cannot be explained by the different age structures in East and West. The average age of the population in East Germany is four years older than its Western counterpart, but the differences in heart failure-related parameters were similar after standardisation for age and were similar in different age groups.

"A possible explanation for our findings may be found in the varied prevalence of risk factors that impact heart failure development, progression and thereby hospitalisation," said Professor Dörr. "In fact, previous research has shown that, for example, hypertension,4 diabetes,5 and obesity6 are much more common in East than in West Germany."

"Moreover, diversities in the structure of patient care may explain the differences, at least in part," he added. "It can be assumed that not all structures and pathways of the national healthcare system have yet been completely adopted in both parts of Germany."

Professor Dörr concluded: "More research is needed to explain the huge differences observed between East and West Germany. Furthermore, it is of great interest to find out whether such regional differences exist in other European countries. Ultimately, the aim should be to develop and implement solutions that improve heart failure care across Europe in order to mitigate this devastating and deadly disease."

Researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have discovered a mechanism controlling the development of a type of liver cancer. This study, published today in the Proceedings of the National Academy of Sciences (PNAS), partly funded by the Spanish Association Against Cancer, has identified a protein that, when blocked, dramatically reduces the impact and progression of this type of cancer, called cholangiocarcinoma. This work has been possible because CNIC researchers have developed an animal model where alterations in the production of bile acids have been proved to cause this type of tumor.

Liver cancer is the fifth most frequent cancer and the second main cause of cancer-related deaths worldwide. Cholangiocarcinoma, the second most common liver cancer, starts in the bile ducts and has a clinically symptomless progression. Because there are no early markers, most patients are diagnosed at an advanced stage and die due to the spread of cancer or metastasis.

In this study, led by Guadalupe Sabio, Alfonso Mora, and Roger J. Davis, mice whose livers do not contain the JNK1 and JNK2 proteins have been bred. "These proteins are activated when we overeat and are partly responsible for excess fat being stored in the liver (i.e. - fatty liver or steatosis), and for the development of insulin resistance," explained Dr. Sabio. The proteins are, therefore, "very significant for obesity and diabetes studies," she added.

Researchers also found that these two proteins control the production of bile acids in the liver, which are essential for proper fat digestion and the absorption of fat-soluble vitamins (A, D, E and K). "A lack of JNK1 and JNK2 in the liver leads to changes in the enzymes responsible for metabolizing cholesterol and bile acids," said Dr. Mora. In the analyzed mice, "we have observed excess blood levels of bile acids."

Researcher Elisa Manieri explained that, over time, this accumulation of bile acids has a "toxic effect" on the liver. Bile ducts begin to proliferate excessively, triggering the formation of multiple cholangiocarcinomas with clinical markers, which are remarkably similar to those of patients with this type of cancer. In fact, "it is the first time that we have found the increase of a cholangiocarcinoma patient marker in mice models." This indicates that these mice could offer new clues to assess novel cholangiocarcinoma therapies.

This model has allowed CNIC researchers, in collaboration with the laboratory of Roger J. Davis at the University of Massachusetts School of Medicine (USA), to find a protein playing a key role in this tumor process, PPARα. The protein regulates the metabolism of bile acids and liver lipids. According to Dr. Mora, the mice lacking PPARα "have significantly fewer tumors or none at all."

Although it is still not known if these data can be extrapolated to human patients, the fact that this first animal model exists will allow the study of a type of tumor that can still only be diagnosed in its very late stages, when metastases have already happened.

Earlier studies had shown that JNK blockading prevented the development of steatosis in the liver. This is why a variety of clinical trials with inhibitors of these proteins have been launched. The researchers believe that the new findings are a "wake-up call" for these drugs. However, Dr. Sabio said we need to be cautious since "a continuous inhibition of JNK can lead to undesirable side effects."

Even though this work has only been trialed in mice, researchers point out that we have to be careful and stay alert as to the results in the livers of patients undergoing treatment with these new drugs. The study has partly been funded by the Spanish Association Against Cancer and the Leonardo Grant for Researchers and Cultural Creators 2017, awarded to Dr. Sabio by the BBVA Foundation.

Exercise can slow or prevent the development of macular degeneration and may benefit other common causes of vision loss, such as glaucoma and diabetic retinopathy, new research suggests.

The new study from the University of Virginia School of Medicine found that exercise reduced the harmful overgrowth of blood vessels in the eyes of lab mice by up to 45%. This tangle of blood vessels is a key contributor to macular degeneration and several other eye diseases.

The study represents the first experimental evidence showing that exercise can reduce the severity of macular degeneration, a leading cause of vision loss, the scientists report. Ten million Americans are estimated to have the condition.

"There has long been a question about whether maintaining a healthy lifestyle can delay or prevent the development of macular degeneration. The way that question has historically been answered has been by taking surveys of people, asking them what they are eating and how much exercise they are performing," said researcher Bradley Gelfand, PhD, of UVA's Center for Advanced Vision Science. "That is basically the most sophisticated study that has been done. The problem with that is that people are notoriously bad self-reporters ... and that can lead to conclusions that may or not be true. This [study] offers hard evidence from the lab for very first time."

The Benefits of Exercise

Enticingly, the research found that the bar for receiving the benefits from exercise was relatively low - more exercise didn't mean more benefit. "Mice are kind of like people in that they will do a spectrum of exercise. As long as they had a wheel and ran on it, there was a benefit," Gelfand said. "The benefit that they obtained is saturated at low levels of exercise."

An initial test comparing mice that voluntarily exercised versus those that did not found that exercise reduced the blood vessel overgrowth by 45%. A second test, to confirm the findings, found a reduction of 32%.

The scientists aren't certain exactly how exercise is preventing the blood vessel overgrowth. There could be a variety of factors at play, they say, including increased blood flow to the eyes.

Gelfand, of UVA's Department of Ophthalmology and Department of Biomedical Engineering, noted that the onset of vision loss is often associated with a decrease in exercise. "It is fairly well known that as people's eyes and vision deteriorate, their tendency to engage in physical activity also goes down," he said. "It can be a challenging thing to study in older people. ... How much of that is one causing the other?"

The researchers already have submitted grant proposals in hopes of obtaining funding to pursue their findings further.

"The next step is to look at how and why this happens, and to see if we can develop a pill or method that will give you the benefits of exercise without having to exercise," Gelfand said. "We're talking about a fairly elderly population [of people with macular degeneration], many of whom may not be capable of conducting the type of exercise regimen that may be required to see some kind of benefit." (He urged people to consult their doctors before beginning any aggressive exercise program.)

Gelfand, a self-described couch potato, disclosed a secret motivation for the research: "One reason I wanted to do this study was sort of selfish. I was hoping to find some reason not to exercise," he joked. "It turned out exercise really is good for you."

Leaving hospital can be a confusing and sometimes risky time for patients who take medication, with an estimated 44% experiencing medicine-related problems once they get home. New research from the University of Bath suggests the most helpful and timely medicine-related support is provided by hospital pharmacists, yet few patients are aware that they can turn to their NHS Trust to allay confusion and stay safe.

The Bath study explored the experiences of 40 patients or their carers using various hospital-based telephone medicines information services. It found that patients who have called a service regard it as uniquely placed to answer medication queries arising after hospital discharge. After using the service, patients said the helpline service was quicker to access than their GP and often more helpful.

But although 52% of NHS Trusts currently provide a medicines helpline, few discharged patients seem to know of their existence, resulting in extremely low usage.

Matt Williams, the Bath PhD student who led the research said: "A typical hospital that discharges over 100 patients every day will have 30 to 40 patients with a potential need to call the helpline, yet they might get just one call a day.

"If people don't know the service exists, they either do nothing when problems arise or they go to their GP, use the emergency services or turn to the people around them or Google for non-expert and potentially unreliable advice. Yet they could resolve their problem with a simple phone call, which is quicker and easier for both the person and the NHS."

Dr Matthew Jones, lecturer in pharmacy practice at the university, explained that patients often experience big changes to their medicine regimen when they are discharged from hospitals, and it's common for them to find there are gaps in their knowledge.

He said: "They might have questions about side effects, correct dosage or potential interactions between medications. Getting the right information can help them avoid harm. It can also draw attention to mistakes that have been made with their medicines."

Helplines have been established to help meet the NHS's priority to improve patients' transitions of care, so people can better manage their own health. Study participants called for their local helpline to be extended to cover evenings and weekends.

A second study from the Bath team finds that hospital pharmacists who provide a hospital medicines helpline service are aware that it is a valuable resource for patients but regard it as under-resourced.

"There is concern among pharmacists that if they advertise the service more widely, they will not be able to cope with the influx of enquiries. This is completely understandable at a time when NHS staff are so stretched. To benefit as many patients as possible, pharmacists need guarantees they will be given time to help everyone who calls" said Dr Jones.

According to the results of research commissioned in 2018 by the UK Department of Health and Social Care, 237 million medication errors occur in the NHS in England every year. Of these, 66 million are of potential clinical significance. Avoidable adverse drug reactions cause around 700 deaths per year and cost the NHS an estimated £98.5-million per year.

A study in 2017 found that discharged patients were not reliably warned of possible problems that could arise from their medications. Of the people involved in the NHS Patient Survey Programme, 43% said a member of staff did not tell them about any side effects to look out for.

Some discharged patients also experience medicines-related errors, such as prescribing mistakes and incorrect or missing information on discharge summary documents. As a result, 26% of discharged patients seek help relating to their medication, mainly from their GP.

Dr Jones said: "It's important that all patients discharged from hospital can easily get timely and expert advice about their medicines. Different areas currently do this in different ways, which is one reason why the public doesn't know about the services that are there to help them. In addition, the government recently announced a new Discharge Medicines Service, which will allow people to seek help from their community pharmacy. The NHS should decide what is the best way to help discharged patients and then ensure that this is provided and advertised by every hospital."

Scientists at Hokkaido University and collaborators have identified how inflammatory changes in tumors caused by chemotherapy trigger blood vessel anomalies and thus drug-resistance, resulting in poor prognosis of cancer patients. Through mice experiment, the team also found that the combined usage of an inhibitor and anticancer drug makes chemotherapy more effective.

Chemotherapy is often chosen for treating inoperable cancers, such as locally advanced and metastasis cases. It is, therefore, essential to unravel drug-resistance in this treatment, which has been a major factor in making cancer malignant and causing metastasis.

Tumor blood vessels play a key role in cancer progression because they carry nutrients and oxygen to tumors and serve as pathways for metastasis. It had been generally believed that tumor endothelial cells (TEC) lining tumor blood vessels did not acquire drug-resistance. However, several years ago, the group's mice experiments showed TEC can obtain various anomalies, suggesting blood vessels, as well as cancer cells, can contribute to making tumors drug-resistant. For example, the group demonstrated for the first time that TEC in blood vessels resist paclitaxel - a chemotherapy medication used for second-line treatment of urothelial cancer - due to the expression of ABCB1 which pumps out the drug from blood vessels.

However, much remains unknown about how human blood vessels are involved in cancer acquiring drug-resistance.

To help unravel this mystery, the group first analyzed tumor tissue samples from urothelial cancer patients before and after they underwent first-line chemotherapy. They found ABCB1 expression was increased in TEC in blood vessels of more than 60 percent of patients who received chemotherapy, and that their prognoses were poorer than patients whose ABCB1 expression remained the same after the treatment.

In addition, they analyzed TEC in blood vessels and bladder cancer cells to study how chemotherapy affects ABCB1 expression. The results showed that the increased secretion of interleukin-8 (IL-8) in cancer cells after chemotherapy caused inflammatory changes, increasing the ABCB1 expression in TEC. In another experiment, mice with urothelial cancer administered with the ABCB1 inhibitor together with paclitaxel showed suppressed formation of new blood vessels and thus metastasis to the lung.

"Our study provides evidence, for the first time in humans, that inflammatory changes in tumors can cause drug resistance in cancer blood vessels," says Kyoko Hida of Hokkaido University who led the group. "These findings could help devise new treatment strategies, such as the development of inhibitors targeting ABCB1 and IL-8, to suppress drug resistance and improve prognosis."

Women who experience high blood pressure during pregnancy are more likely to develop heart disease and heart failure in later life, according to an international team of researchers.

Between 1-6% of all pregnancies in Western countries are affected by high blood pressure, which usually returns to normal after giving birth. This condition is known as gestational hypertension, or pregnancy-induced hypertension. It differs from pre-eclampsia in that traces of protein are not found in the urine. Clinicians increasingly recognise that women who have had gestational hypertension are more likely to develop cardiovascular disease in later life.

However, studies of different kinds of cardiovascular disease, such as heart disease and heart failure, have found mixed results. To examine these links further, an international team of researchers conducted a systematic review and meta-analysis of 21 studies involving a total of 3.6 million women, 128,000 of who previously had gestational hypertension. This type of study is a way of combining data from all existing relevant studies, allowing researchers to compare and consolidate results from often-contradictory studies to reach more robust conclusions.

The results are published in the Journal of the American Heart Association.

The researchers found that women who experienced high blood pressure during their first pregnancy were at 45% higher risk of overall cardiovascular disease and 46% higher risk of coronary heart disease compared to women who did not have high blood pressure in pregnancy. Women with one or more pregnancies affected by high blood pressure were at 81% higher risk of cardiovascular disease, 83% higher risk of coronary heart disease and 77% higher risk of heart failure.

"When we looked at all the available research, the answer was clear: women who develop high blood pressure during pregnancy - even when it doesn't develop into pre-eclampsia - are more likely to develop several different kinds of cardiovascular disease," said senior author Dr Clare Oliver-Williams from the Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge.

The study adds to growing evidence of the relationship between pregnancy and subsequent risk of cardiovascular events. Recurrent miscarriages, preterm birth, foetal growth restriction and pre-eclampsia have all previously been linked with a greater risk of heart disease.

The researchers say it is not entirely clear why gestational hypertension is associated with heart disease in later life. However, they suggest it may be that high blood pressure in pregnancy causes lasting damage that contributes to cardiovascular disease. Alternatively, women who develop gestational hypertension may have a pre-existing susceptibility to cardiovascular disease that is revealed due to the large demands that pregnancy places upon women's bodies.

Dr Oliver-Williams added: "It's important that women know that it isn't their fault that they developed high blood pressure in pregnancy, and developing heart disease isn't a foregone conclusion. Women who have experienced gestational hypertension may have been dealt a tough hand, but it's how they play those cards that matters the most. Small positive changes can really help. They can be as simple as eating more fruit and vegetables, small bouts of regular exercise and finding time to unwind, if that's possible with kids around."

CLEVELAND, Ohio (July 1, 2020)--Perimenopause is a time when women become more vulnerable to a number of health problems. A new study based on data from the Canadian Longitudinal Study on Aging identified menopause as a risk factor for the development of metabolic syndrome or some of its components, including hypertension, central obesity, and high blood sugar. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

The incidence of metabolic syndrome increases with age and, in Canada, is as high as 38% in women aged 60 to 79 years. Understanding what causes metabolic syndrome is important because this condition increases the risk of heart disease and cancer, two of the leading causes of death in women.

Some previous studies have suggested an association between the onset of menopause and the development of metabolic syndrome, independent of aging. This study analyzed data from more than 10,000 women aged 45 to 85 years who participated in the Canadian Longitudinal Study on Aging, and found a positive association between menopause and an increased risk of metabolic syndrome.

The good news, however, is that lifestyle interventions targeted at women with metabolic syndrome have proven effective in preventing type 2 diabetes mellitus and cardiovascular risk. Age at menopause and hormone therapy use have also been identified as possible modifiers of this relationship, although additional studies are required to better quantify their effect.

Study results appear in the article "The effect of menopause on metabolic syndrome: cross-sectional results from the Canadian Longitudinal Study on Aging."

"These results reaffirm the previously identified link between menopause and metabolic syndrome. Given the increased cardiovascular risk associated with metabolic syndrome and that heart disease remains the number one killer of women, this study highlights the importance of cardiovascular risk assessment and risk reduction strategies in midlife women," says Dr. Stephanie Faubion, NAMS medical director.

A quality improvement initiative in the Neonatal Intensive Care Unit (NICU) at Children's National Hospital led to a significant reduction in treatment with intravenous vancomycin, an antibiotic used for resistant gram positive infections, which is often associated with acute kidney injury. The findings, published in the journal Pediatrics, show the initiative reduceed vancomycin use in patients by 66%, and the NICU has sustained the reduction for more than a year.

Vancomycin is a broad-spectrum antibiotic often used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. It's one of the most commonly prescribed antibiotics in NICUs, but its overuse poses an increased risk of morbidity. Benchmarking data showed that in 2017, vancomycin use at Children's National Hospital was significantly higher than use at peer institutions, suggesting there was likely an opportunity to optimize use of this drug.

The intervention program was led by Rana Hamdy, M.D., M.S.C.E., M.P.H., an infectious diseases specialist at Children's National, Lamia Soghier, M.D., medical unit director of the Children's National NICU, and other team members from neonatology, infectious diseases, pharmacy, nursing and quality improvement. The team accomplished the perscribing reduction by sequentially implementing a four-step approach involving interdisciplinary team building and provider education, pharmacist-initiated 48-hour time-outs, clinical pathway development and prospective audit with feedback.

"Our interdisciplinary quality improvement team was devoted to this project and implemented interventions that, early on, led not only to reduction in vancomycin use, but to better outcomes in our patients with fewer episodes of vancomycin-associated acute kidney injury," said Dr. Hamdy. "This led to early buy-in from the prescribers, ultimately changing the culture of antibiotic prescribing in the NICU."

Following the NICU's intervention program to improve patient safety, vancomycin use in patients decreased from 112 days of therapy per 1,000 patient-days to 38 days of therapy per 1,000 patient-days. During the intervention program, the researchers noted that this was "the first work to show a significant change in vancomycin-associated acute kidney injury in neonates."

Four key interventions were sequentially implemented to successfully achieve and sustain the reduction in vancomycin use. Intervention 1 was the development of an interdisciplinary and provider education team that addressed institutional antibiotic prescribing practices.

Intervention 2, a pharmacist-initiated 48-hour time-out, involved clinical pharmacists identifying patients who have been on antibiotics for ? 48 hours and encouraged their providers to either discontinue vancomycin or to switch to a narrow-spectrum antibiotic. Intervention 3 consisted of the development of new clinical pathways including discontinuing vancomycin in infants at low-risk for MRSA. Lastly, intervention 4, antimicrobial stewardship program (ASP) prospective audit and feedback, involved an ASP member reviewing all NICU vancomycin orders and issuing appropriate recommendations for NICU providers and pharmacists to be carried out within 24 hours.

This project was taken on as part of Children's National Quality Improvement and Leadership Training (QuILT) course sponsored by the Quality & Safety Department. This notable work was highlighted in the 2019 annual Quality and Safety report and by the Magnet program as an exemplary example of nursing-physician partnership working to improve patient care.

The associated article, "Reducing Vancomycin Use in a Level IV Neonatal Intensive Care Unit," will be published July 1 in Pediatrics. The lead author is Dr. Rana Hamdy is an infectious disease specialist and director of the Antimicrobial Stewardship Program. Twenty notable co-authors are also from Children's National.

WASHINGTON, June 30, 2020 -- While the use of face masks in public has been widely recommended by public health officials during the current COVID-19 pandemic, there are relatively few specific guidelines pertaining to mask materials and designs. A study from Florida Atlantic University, in the Physics of Fluids, from AIP Publishing, looks to better understand which types are best for controlling respiratory droplets that could contain viruses.

Siddhartha Verma and his team experimented with different choices in material and design to determine how well face masks block droplets as they exit the mouth. Using a laser to detect droplets as they were coughed and sneezed out of a mannequin head, the group was able to map out the paths of droplets and examine how different designs and materials alter that path.

The authors note the need for further quantitative analysis but were aware of the power of more straightforward visualization.

"While there are a few prior studies on the effectiveness of medical-grade equipment, we don't have a lot of information about the cloth-based coverings that are most accessible to us at present," said Verma. "Our hope is that the visualizations presented in the paper help convey the rationale behind the recommendations for social distancing and using face masks."

The approach draws on a laser sheet setup that is a mainstay for those studying fluid mechanics, which Verma compares to seeing dust particles in a beam of sunlight.

"The main challenge is to represent a cough and sneeze faithfully," he said. "The setup we have used a simplified cough, which, in reality, is complex and dynamic."

LINK TO VIDEO: https://www.youtube.com/watch?v=_k7AUHPY2Pk

The group found that loosely folded face masks and bandanna-style coverings reduced the distance traveled by the droplet jets between 1/8 to 1/2 respectively of that for an uncovered cough. However, well-fitted homemade masks with multiple layers of quilting fabric and off-the-shelf cone style masks proved to be the most effective. Some leakage notwithstanding, these masks reduced the number of droplets significantly.

When without a mask, the mannequins were projecting droplets much farther than the oft-cited 6 feet in social distancing guidelines.

Verma said the group looks to continue studying the complex interplay that can involve droplet evaporation, ambient airflow and properties of the respiratory fluid ejected that lead to how droplets behave.

"It is also important to understand that face coverings are not a 100% effective in blocking respiratory pathogens," he said. "This is why it is imperative that we use a combination of social distancing, face coverings, hand-washing and other recommendations from health care officials until an effective vaccine is released."

WASHINGTON, June 30, 2020 -- Spiders -- what are they good for? The answer, it turns out, is more than just insect control.

Spider silk is useful for a variety of biomedical applications. It exhibits mechanical properties superior to synthetic fibers for tissue engineering, and it is not toxic or harmful to living cells.

One unexpected application for spider silk is its use in the creation of biocompatible lenses for biological imaging applications. A team of researchers from Tamkang University and National Yang-Ming University in Taiwan describes the feasibility of creating lenses capitalizing on the properties of natural spider silk material in the Journal of Applied Physics, from AIP Publishing.

A spider can spin several different types of silks, each with different properties and functions. To create the spokes of their web, spiders use a type of silk known as dragline silk.

"Dragline silk is an interesting natural material because of its significant features, such as high elasticity, great toughness and large tensile strength," said Cheng-Yang Liu, one of the authors on the study and a professor at National Yang-Ming University. Compared to its weight, the strength of dragline silk is greater than steel.

The authors collected smooth, uniform dragline silk from Pholcus phalangioides spiders, commonly known as daddy longlegs, and dripped a resin onto the silk fiber. As the resin condensed on the fiber, the wetting properties of the silk naturally formed it into a dome shape, which they found could be used as an optical lens. The mechanical and optical properties of the silk also make it ideal for supporting the lens.

When they shined a laser onto the lens, it generated a high-quality photonic nanojet -- a type of beam that can provide large-area, super-resolution imaging for biomedical applications. By tuning the length of time the silk spends under the resin drip, the size of the dome lens can be changed, allowing the photonic nanojets to be optimized for the desired type of imaging.

"The dome lens with flexible photonic nanojets is suitable for imaging the nanoscale objectives in different depths within biological tissue," Liu said.

After additional testing, the researchers hope this type of spider silk-based lens can be used to deliver light for biological imaging and operation.