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PORTLAND, OR - Cancer patients with no health insurance or those enrolled in Medicaid, the federal low-income health insurance program, see smaller survival benefits from experimental therapies in clinical trials, according to study results published today in JAMA Network Open.

The SWOG Cancer Research Network study is the first to examine whether treatment effects from randomized cancer clinical trials with positive findings apply to important demographic and insurance subgroups. The finding that cancer clinical trial patients with no or low insurance don't get the same benefits of experimental therapies as patients with private insurance - regardless of sex, age or race or ethnicity - supports efforts in Congress to expand insurance coverage.

These efforts include the CLINICAL TREATMENT Act, a bipartisan bill introduced in February in the House of Representatives that guarantees coverage of the routine care costs of clinical trial participation for Medicaid enrollees with a life-threatening condition. Nearly 20 percent of Americans receive health insurance through Medicaid. The bill was introduced by U.S. Rep. Ben Ray Luján (D-NM) and U.S. Rep. Gus Bilirakis (R-FL) and has the backing of more than 100 organizations, including the American Society of Clinical Oncology, the American Cancer Society, and the American Medical Association.

"A patient's insurance coverage seems to be related to the extent to which they benefit from new experimental treatments tested in trials," said Joseph Unger, PhD, a SWOG health services researcher and biostatistician based at Fred Hutchinson Cancer Research Center and the study leader. "Our findings highlight the importance of policies that would provide more Americans insurance coverage, and underline the importance of improving that coverage."

It's difficult to measure the impact of insurance status, or any demographic factor, on cancer clinical trial outcomes. Most cancer trials do not enroll enough patients to accurately determine whether treatment outcomes differ based on individual factors such as health insurance status. The SWOG study is unique because it taps the network's vast clinical trials database spanning decades, and used insurance status data collected for patients as part of those trials. Founded in 1956, SWOG is a cancer clinical trials network funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and a member of the oldest and largest publicly-funded research network in the nation.

Unger and his team examined data from 19 SWOG phase III randomized treatment trials that enrolled patients between 1984 and 2012 and followed those patients up to five years after their trial treatment. The 19 trials tested drugs for a number of cancers, from breast to lung. These were "positive" trials - studies that found patients who received experimental trial drugs had better survival than patients who received standard treatments.

The analysis resulted in a pool of 10,804 patients. The team then assessed whether the overall survival rates, as well as the progression- or relapse-free survival rates, differed by age, sex, race and ethnicity, and insurance status.

What they found: Patients 65 or older, younger than 65, male, female, minority, non-minority, and with private insurance who received experimental trial drugs all, on average, lived longer compared to patients who took the standard treatments. The only group that didn't get such a strong survival benefit from the new drugs were patients uninsured or enrolled in Medicaid.

This disparity, Unger said, could be due to several factors. A big one: Insurance status tends to reflect socioeconomic status.

"People with fewer financial resources have access to fewer healthcare resources, which can have a persistent, negative influence on their health," Unger said. "Patients in trials having no or limited insurance may not have the financial means to pay for the extra supportive treatments or post-trial cancer treatments that help people live longer. This could be especially meaningful for understanding treatment benefits if experimental therapy requires more supportive care or is more difficult to adhere to than standard treatment."

NEW YORK, April 30, 2020 (print edition) -- A new study from researchers at The Graduate Center, CUNY; College of Staten Island; and The University of Helsinki provides insight into what may be occurring in the brains of people with certain neurological conditions, including autism spectrum disorder, epilepsy, and schizophrenia. The work could point toward useful therapies in treating these disorders.

The newly published findings in Current Biology explain why the African naked mole-rat, one of only two mammals to lead eusocial lives, never leave their colony to start new families and pile on top of each other in large groups to sleep inside their nest. Researchers found that these animals have a mutation of the gene for the KCC2 protein, which normally helps inhibit neurons. The variant, called R952H, causes the naked mole-rat to have a harder time suppressing brain activity, so that breathing in uninhibited levels of oxygen when the animals are inactive causes their brains to race and leads to a possible panic response and seizures. But the higher levels of carbon dioxide in their tightly packed nests inhibits brain activity, preventing this response. The researchers confirmed this connection by finding a similar genetic variant in the Damaraland mole-rat, the only other eusocial mammal.

Human brains also require a certain amount of inhibition to operate properly, and KCC2 protein function is developmentally regulated in humans and most other mammals. The mutation of this protein can be responsible for a glitch in brain activity suppression. Interestingly, the R952H variant thought to be responsible for this glitch in mole -rats has been reported in people with autism spectrum disorders, schizophrenia, and epilepsy.

"The link to humans with the R952H is what drives a lot of our questions," said Daniel McCloskey, a psychology professor at The Graduate Center and College of Staten Island. "This has opened our eyes to the idea that some people around us may be more sensitive to the air we breathe and how we breathe it. Maybe there is a fix that can help these people feel more comfortable."

The study proposes that the naked mole-rat could be used as a model to find treatments for people with this genetic difference. Conjunction therapy, in which carbon dioxide or drugs that lower neuron pH is added to an existing treatment regimen, may provide some benefits to individuals with certain neurological disorders and the R952H variant, the study authors noted.

DALLAS, April 30, 2020 -- Treatment for heart failure should take into consideration a patient's social determinants of health - their overall living environment, socio-economic status, as well as the needs of unpaid family caregivers, according to two new scientific statements from the American Heart Association, published simultaneously today in the Association's flagship journal Circulation.

Heart failure, which affects 6.5 million Americans, is a slow, progressive disease in which the heart does not pump blood effectively. Although there is no cure, people with heart failure can live full lives with the help of medication, lifestyle changes and social support. Caregivers are needed as the disease progresses and when an individual is no longer able to manage the activities of daily living or complex medical regimens.

The scientific statement, "Addressing Social Determinants of Health in the Care of Patients with Heart Failure," provides an overview of scientific research that demonstrates how the county where a patient lives, personal and social factors, such as insurance status, disability status, race, ethnicity and income inequality, may impact patients from receiving state-of-the-art care for their heart failure.

"Patients who don't have insurance coverage, enough to eat, struggle with transportation, don't have a safe place to be physically active, can't afford medications and/or have less education and/or insurance coverage may have significantly poorer heart failure outcomes, compared to people who don't experience those factors," said Connie White-Williams, Ph.D., R.N., chair of the statement writing committee, senior director of Nursing Services and the Heart Failure Transitional Care Clinic at the University of Alabama at Birmingham Hospital. "It's important that we ask patients about the life issues and challenges they may be facing; these issues have a direct impact on the patient's ability to adhere to any care plan."

To help overcome non-medical barriers to effective care for people with heart failure, the statement suggests a best practice scenario where an interprofessional health care team works together to support the patients, their families and caregivers. This support should address the numerous life challenges that can impact health outcomes, such as the patient's living situation, caregiver availability, ability to pay for medications and how well a patient and their caregiver understand medical information.

"Addressing social determinants of health can be resource-intensive, and many clinical practices do not have the resources nor are they set up to deal with these challenges. However, when nurses, physicians, social workers, pharmacists and mental health professionals work together, an effective plan of care can be designed to keep heart failure patients healthier and out of the hospital," White-Williams said. "This is a model we should be working towards implementing whenever possible."

The statement urges health care providers to routinely discuss a heart failure patient's overall living situation to identify challenges that affect their medical care. Whenever possible, health care providers should:

assist patients seeking insurance coverage, financial assistance, affordable housing or employment;

present health information in formats tailored to meet each individual's language, level of education and health literacy;

support nurse-led collaborative clinics that assist patients in becoming better stewards of their own health;

use medication access programs to help provide drugs out of patients' financial reach; and

partner with local food banks to help provide groceries to food-insecure patients.

"Recognizing the importance of social determinants of health is a critical first step toward getting health systems engaged in developing approaches to mitigate the many adverse consequences of these factors in different settings," said White-Williams.

A related scientific statement, "Family Caregiving for Individuals with Heart Failure" presents an overview of the challenges faced by unpaid family members who serve as caregivers for patients with heart failure.

Because heart failure is a progressive disease with alternating periods of stability, caregiver demands change over time. Following an initial diagnosis of heart failure, caregivers may need to provide emotional support to help patients cope with their heart failure diagnosis, potential social isolation and loss of independence.

As the disease progresses, patients often need help with the activities of daily living, such as bathing, toileting, dressing, medication adherence and navigating the health care system. In advanced heart failure, caregivers are often engaged to assist with management of intensive care therapies such as mechanical circulatory support that would previously have been undertaken by health care professionals in clinical settings.

"There is a critical need for health care providers to clearly understand the demands of caregiving and how these change throughout the trajectory of heart failure. Development of tools to screen and identify caregivers who are at high risk for depression and distress are also needed," said Lisa Kitko, Ph.D., R.N., chair of the family caregiving writing committee, and associate professor and associate dean of graduate education at the Pennsylvania State University College of Nursing in University Park, Pennsylvania.

"It is also important to assess caregiver capabilities, including their motivation to provide care; their physical, sensory, motor and cognitive ability to perform required tasks; their level of distress and depression. This includes making referrals to obtain supportive services, such as counseling and respite care on behalf of the caregiver," said Kitko.

Health care providers should include caregivers when working with the patient to make difficult decisions, such as whether to surgically implant medical devices designed to help the heart pump more effectively or deciding when it is time to deactivate these devices and progress to palliative or hospice care. "Palliative and/or hospice care providers may also have resources to support caregivers," said Kitko.

It is estimated that caregivers spend an average of 22 hours per week caring for patients with heart failure, and thus, they play an integral and instrumental role in providing care. Unpaid caregivers often experience loss of income, benefits and career opportunities, which can be financially burdensome to the entire family. These costs may be disproportionately borne by older adults, women and persons in underserved race/ethnic groups already at higher risk for financial insecurity.

In addition to the financial costs, significantly higher physical and psychological health risks, such as social isolation and disruption of outside relationships, have been observed among people caring for family members with chronic illnesses such as heart failure.

"In our current health care system, there is a lack of incentives for clinicians to evaluate caregiver needs and offer direct support.

The largest barrier is the lack of payment and reimbursement mechanisms that would allow clinicians to provide direct support to caregivers," said Kitko. "Other barriers include a lack of systematic mechanisms to identify caregivers and make referrals for those with the highest distress and unmet needs; medical record systems that can accommodate caregiver assessment, intervention and tracking; limited funding for community-based agencies that provide caregiver services; minimal time for clinical interactions with patients, which limits the ability address caregiver concerns or distress; and lack of clear guidelines for caregiver support provision."

WASHINGTON--The rate of heart attacks, strokes and other cardiovascular complications has improved among people with diabetes over the past 20 years, narrowing the gap in cardiovascular mortality rates between individuals with and without diabetes, according to a new study published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

More than 463 million adults worldwide have diabetes, according to the International Diabetes Federation. Adults with diabetes have a two- to three-fold increased risk of heart attacks and strokes compared to adults who do not have the condition, according to the World Health Organization.

"Our study found that the rate of cardiovascular complications among individuals with diabetes has declined over the past two decades," said senior author Timothy M.E. Davis, F.R.A.C.P, of the University of Western Australia and Fremantle Hospital in Fremantle, Australia. "While we've seen improvements in cardiovascular disease outcomes in the general population during the same time period, the gains in individuals with diabetes outpaced the general population during that timeframe."

The researchers analyzed data from two phases of the Fremantle Diabetes Study, which took place 15 years apart. The first phase, which ran from 1993 to 2001, compared data on 1,291 individuals with type 2 diabetes to 5,159 residents without the condition. During the second phase from 2008 to 2016, researchers collected data from 1,509 participants with type 2 diabetes and compared outcomes to 6,036 individuals who did not have the condition.

The researchers used a database of hospital records and death records for Western Australia to identify cardiovascular complications and deaths among study participants.

Individuals with diabetes in the Fremantle Diabetes Study's second phase were less likely to experience a heart attack or stroke, be hospitalized for heart failure, or be hospitalized for a lower extremity amputation than their counterparts in the first phase.

"While the outlook for people with diabetes in developed countries is improving significantly, we remain concerned that the death rate from all causes among people with diabetes is worse than the general population," Davis said. "The trend shows we still have to monitor conditions like cancer and dementia that may become an issue for people with diabetes later in life."

Scientists from the University of Gothenburg, Sweden, have found a new method of reducing human body weight and fat mass using weighted vests. The new study indicates that there is something comparable to built-in bathroom scales that contributes to keeping our body weight and, by the same token, fat mass constant.

The researchers hypothesized that loading the vests with weights would result in a compensatory body-weight decrease. Sixty-nine people with a body mass index (BMI) of 30-35, the lowest obesity category, took part in the clinical study. Their instructions were to wear a weighted vest eight hours a day for three weeks, and otherwise live as usual.

All the study participants wore weighted vests but, by drawing of lots, they were assigned to one of two groups. The control group wore only light vests weighing 1 kg, while the treatment group wore heavy vests weighing some 11 kg. When the three weeks had passed, the experimental subjects who wore the heavier vests had lost 1.6 kg in weight, while those wearing the light vests had lost 0.3 kg.

"We think it's very interesting that the treatment with the heavier weighted vests reduced fat mass while muscle mass simultaneously remained intact," says Professor Claes Ohlsson of Sahlgrenska Academy, University of Gothenburg.

"The effect on fat mass we found, from this short experiment, exceeded what's usually observed after various forms of physical training. But we weren't able to determine whether the reduction was in subcutaneous fat (just under the skin) or the dangerous visceral kind (belly fat) in the abdominal cavity that's most strongly associated with cardiovascular diseases and diabetes," says Professor John-Olov Jansson of Sahlgrenska Academy, University of Gothenburg.

In previous animal studies published in 2018, the scientists showed that there is an energy balance system that endeavors to keep body weight constant: the "gravitostat," as they have dubbed it. In mice, this regulation takes place partly by influencing appetite. To work, the system must contain a kind of personal weighing machine. The researchers' new clinical study shows that similar built-in scales exists in humans as well.

If people do a lot of sitting, what seems to happen is that the reading on our personal scales falls too low. This may explain why sitting is so clearly associated with obesity and ill-health. Weighted vests can raise the reading on the scales, resulting in weight loss.

Many questions about how the gravitostat works remain for the researchers to answer. Aspects they want to study include whether, in wearers of weighted vests, changed energy expenditure, appetite and mobility help them to lose weight. The scientists also want to see whether the weight reduction continues for the vest wearers over periods longer than three weeks, and whether the dangerous visceral fat is reduced by the treatment.

A recently completed study indicates that smoking by pregnant mothers caused roughly an 1.5-fold asthma risk in their offspring at the ages between 31 and 46.

Exposure to cigarette smoke is known to increase the risk of asthma in childhood, but research findings on its later effects are scarce.

A study published in the European Respiratory Journal investigated 5,200 individuals born in Northern Finland in 1966. The mother's smoking during pregnancy resulted in an approximately 1.5-fold asthma risk in the child at the ages between 31 and 46. The risk was higher for those who had reported suffering from respiratory symptoms previously or who were carriers of the RUNX-1 susceptibility gene.

"The findings may point to the early vulnerability of the airways and permanent harm caused by cigarettes," says Docent Sanna Toppila-Salmi from the University of Helsinki and the Hospital District of Helsinki and Uusimaa.

According to Toppila-Salmi, families planning for a pregnancy and expectant mothers should be encouraged to give up smoking. This would lower the risk of adult-onset asthma in their children and improve the health of the airways.

The study was carried out collaboratively by the University of Helsinki, the University of Oulu and the National Institute for Health and Welfare.

A group of our cancer and mathematics researchers at Houston Methodist have developed a clinically-applicable mathematical model to predict patient outcomes to cancer immunotherapy. Vittorio Cristini, Ph.D., and colleagues report in the April 29 issue of Science Advances that they designed this model in a way that allows for a usable quantitative tool to clinical practice. What makes this model a bit more innovative is that it can calculate a predicted response on a per-patient basis, providing a framework for engineered individual treatment strategies.

They obtained CT-scan imaging data of tumors from before, during, and after immunotherapy in 121 patients treated with checkpoint inhibitor immunotherapy, that were then analyzed using the model to quantify patient-specific indicators of therapeutic response. They found that two mathematical markers that correlate with one or more biologically or clinically relevant parameters, such as anti-tumor immune state and tumor kill rates, were able to identify patient response and survival with high accuracy. Then they validated these results with data from 124 additional patients treated with common checkpoint inhibitor immunotherapies. The model is now being prepared for inclusion in an upcoming clinical trial involving Houston Methodist Cancer Center and MD Anderson Cancer Center.

Sleeping sickness and Chagas disease, caused by the tropical parasites Trypanosoma brucei and Trypanosoma cruzi, constitute a significant socioeconomic burden in low-income countries of sub-Saharan Africa and Latin America, respectively. Drug development for treating these diseases is underfunded. Moreover, current treatments are outdated and difficult to administer, while drug resistance is an emerging concern. In this report, a team of researchers lead by Dr. Grigoris Zoidis at the National and Kapodistrian University of Athens (Athens, Greece), in collaboration with researchers at the Ruder Boskovic Institute (Zagreb (Croatia), and the London School of Hygiene and Tropical Medicine (London, United Kingdom) have attempted to extend the structure-activity relationship (SAR) analysis of a number of lipophilic guanylhydrazone analogues with respect to in vitro growth inhibition of T. brucei and T. cruzi. The synthesis of adamantane-based compounds that have potential as antitrypanosomal agents has been extensively reviewed by the team. The researchers also investigated the critical role of the adamantane ring by synthesizing and testing a number of novel lipophilic guanylhydrazones. The introduction of hydrophobic bulky substituents onto the adamantane ring generated the most active analogues, illustrating the synergistic effect of the lipophilic character of the C1 side chain and guanylhydrazone moiety on trypanocidal activity. In their study, the n-decyl C1-substituted compound G8 proved to be the most potent adamantane derivative against T. brucei with activity in the nanomolar range (EC50=90 nM). Molecular simulations were also performed to better understand the structure-activity relationships between the studied guanylhydrazone analogues and their potential enzyme target.

Keywords: Adamantane, S-adenosylmethionine decarboxylase (AdoMetDC), guanylhydrazones, structure-activity relationships, trypanocidal agents, kernel-based partial least squares regression, szmap, hydration analysis, docking-scoring calculations.

For further information, please visit: http://www.eurekaselect.com/node/179201

Digitization can do a lot in medicine, even save lives. This is shown by the specific case of an 80-year-old patient in Mainz. The passionate Apple Watch wearer showed up in the Chest Pain Unit of the University Medical Center Mainz and complained about typical chest pain, irregular pulse and an intermittent presyncopies - all possible symptoms of coronary artery disease (CAD) and thus possible harbingers of a heart attack. The ECG recorded in the CPU as well as the results from blood testing were normal. Then, the patient presented ECG recordings to the cardiologists, which had previously been made with her watch. These recordings showed signs of marked, so-called ST segment depression - a clear sign for severe coronary ischemia. Based on these recordings the patient underwent an immediate heart catherization, which revealed a severe coronary artery disease such as a main stem stenosis and a bifurcation lesion involving the left anterior descending artery. The mainstem stenosis and the bifurcation lesion were treated successfully with ballooning the arteries and subsequent stent implantation. The patient was discharged symptom-free and in good conditions two days later.

The cardiologists Drexler and Münzel conclude: "As many experts and patients as possible worldwide should know that the Apple Watch ECG app can be used to diagnose cardiac arrhythmias and it may also be able to detect coronary ischemia. When used appropriately, the digital diagnostic aids may prevent myocardial infarctions and save many lives - as in the case of the 80-year-old patient from Mainz. One could say it like this: An Apple a day may keep myocardial infarction away."

Women whose first baby is born at full term, but who experience complications in pregnancy, have an increased risk of preterm delivery (before 37 weeks) in their next pregnancy, finds a study from Norway published by The BMJ today.

The findings suggest that term complications may share important underlying causes with preterm delivery that persist from pregnancy to pregnancy - and could therefore help identify women at increased risk of preterm delivery, despite having had a previous term birth, say the researchers.

Women who deliver at term are generally considered to be at low risk of preterm delivery in later pregnancies, but it is not clear whether pregnancy complications or poor outcomes at birth might increase the risk of preterm delivery.

So researchers based in Norway and in the US set out to explore whether pregnancy complications or poor outcomes after a first term delivery might increase the risk of preterm delivery in the next pregnancy.

Their findings are based on data from Norway's Medical Birth Registry linking first and second pregnancies for 302,192 women between 1999 and 2015.

Term complications included pre-eclampsia (abnormally high blood pressure and excess protein in the urine), placental abruption (when the placenta comes away from the womb), stillbirth, neonatal death (in the first 28 days), and having a small baby (small for gestational age).

The researchers found that women with any of the five complications at term were at substantially increased risk of preterm delivery in their next pregnancy. The conclusion did not change after taking account of potentially influential factors, such as mother's age, pre-pregnancy weight, education level and smoking status.

Compared with having none of the five complications in the first pregnancy, having any one of the complications led to a doubling of preterm risk, while having any two or more complications more than tripled the risk.

The absolute risks for preterm delivery in second pregnancy were 3% with none of the five term complications, 6% after term pre-eclampsia, 7% after term placental abruption, 13% after term stillbirth, 10% after term neonatal death and nearly 7% after term small for gestational age.

This is an observational study, so can't establish cause, and the researchers point to some limitations that may have affected the accuracy of their findings.

However, the results are based on high quality population-based birth data, and were largely unchanged after a range of further analyses, suggesting that they withstand scrutiny.

As such, they conclude that serious complications in pregnancy at term "imply an increased risk not only of recurrence of the same outcome but also of preterm birth in a subsequent pregnancy. These findings might inform antenatal clinical care by helping to identify women at increased risk of preterm delivery."

And they add that further exploration of the causal factors underlying these shared risks "might provide insight into fundamental biological mechanisms that link a broad range of pregnancy complications."

The research, published today in The Lancet Infectious Diseases is the fruit of joint project between investigators from around the world to conduct the largest individual patient data meta-analysis to date under the WWARN umbrella. The study found that artemether-lumefantrine (AL) and other artemisinin-based combination therapies (ACTs) were significantly more effective than quinine, the current recommended treatment. Authors urgently call for further investigation into dose optimisation for pregnant women to ensure the highest possible treatment success.

Pregnant women are particularly susceptible to malaria, with the infection adversely affecting both mother and fetus. An estimated 60% of pregnant women in the world live in malaria endemic regions, with 125 million pregnant women at risk every year. Despite this, expectant mothers have been hugely understudied in antimalarial clinical trials. Typically, this group was excluded from clinical trials due to concerns over drug safety on the fetus, however the last two decades have seen increasing evidence that commonly used malaria treatments are in fact safe. Despite this, there are no agreed guidelines to assess antimalarial drug efficacy during pregnancy.

At present, quinine with clindamycin is the recommended drug to treat women during their first trimester of pregnancy. However, clindamycin is not widely available in malaria-endemic areas and quinine monotherapy is commonly used throughout all trimesters.

In this study, WWARN conducted an individual patient data meta-analysis of existing data from 4,968 pregnant women from 19 studies across 10 countries - representing 92% of patients in the available literature. Pooling and standardising the data from many regions and time-periods into a single dataset for analyses increases the statistical power needed to address key knowledge gaps, particularly when the existing data is sparse. Researchers assessed the efficacy and tolerability of quinine-based treatments and ACTs, including AL, the most commonly used ACT.

Authors found that the efficacy and tolerability of ACTs was better than that for quinine. AL had the best tolerability, but the lowest efficacy in comparison to other ACTs. Authors suggest the lower efficacy may be because dosing of AL is too low and recommend further investigation into dose optimisation.

First author on the study Dr Makoto Saito says: "As the safety of ACTs have been shown previously, the most efficacious drug with fewer side effects should be used to minimise the adverse impact of malaria on mother and fetus. Although the current dosing of ACT for pregnant women may not be optimal, pregnant women no longer have to put up with quinine."

"We found that women in their first pregnancy or with higher malaria parasite burden were at a higher risk of treatment failure and should be carefully monitored"

In high malaria transmission areas, there was recurrence of falciparum malaria in 58.0% of women within 28 days of quinine treatment, while there was 13.8% recurrence after AL treatment. In low transmission areas, both treatments were more efficacious but 33.6% of women treated with quinine had recurrence within 28 days. Regardless of transmission intensity, over 95% of women treated with all other ACTs were free of recurrence.

Presence of gametocytes, the sexual precursor cells of malaria parasites were more frequent after quinine treatment compared with ACTs, this favours the use ACTs as they will be reducing the overall transmission of malaria parasites. Quinine was associated with lower tolerability due to higher risks of side effects such as abdominal pain, nausea and vomiting. This could be further exacerbated by morning sickness in the first trimester, the time during which quinine is recommended. As pregnant women infected with malaria generally have less symptoms than non-pregnant women, they are less likely to tolerate adverse drug events.

Authors caution that updated variable local patterns of resistant to antimalarial treatments should be considered when applying these findings to specific settings, and also both efficacy and tolerability of ACTs need to be re-assessed if a new dosing regimen is proposed for pregnant women.

Prof Philippe Guérin, Director of WWARN and senior author on the study says: "The findings of this study as well as evidence of safety shown in previous research provides compelling evidence that quinine provides lower efficacy and tolerability than ACTs. Further research into drug dosing to ensure optimum treatment effectiveness for both mother and fetus is paramount."

Medical images for a wide range of diseases, including COVID-19, can now be more easily viewed, compared, and analyzed using a breakthrough web-based imaging platform developed by Massachusetts General Hospital (MGH) and collaborating researchers.

The Open Health Imaging Foundation (OHIF) web viewer was originally developed with grant support from the National Cancer Institute's Informatics Technology for Cancer Research (NCI-ITCR) program for use in cancer imaging research and clinical trials, where it is already adopted by several leaders in the field. However, the OHIF Viewer and its underlying Cornerstone libraries and tools can also be used for any disease and are increasingly being used for COVID-19 projects.

"This viewer provides performance that you typically only get from an installed application [software], but we do it through a web browser," says Gordon J. Harris, PhD, the corresponding author of a paper about this viewer in Journal of Clinical Oncology: Clinical Cancer Informatics. "This is a free, open-source extendable platform that is already being used by projects worldwide."

Dr. Harris is director of the 3D Imaging Service at MGH and a professor of radiology at Harvard Medical School. OHIF was founded in 2015 and is led by a team including Dr. Harris and co-author collaborators Chris Hafey, Rob Lewis, Steve Pieper, Trinity Urban, and Erik Ziegler.

The already popular free program is interoperable, commercial grade, user-friendly and requires less technical support than a typical commercial product. The software is "zero footprint," meaning it can be run in a web browser from any computer without any software being downloaded. It can be launched from a web server on a local computer, or in the cloud. It is also accessible for a user to access from multiple locations.

In addition, researchers can freely download, modify, and contribute to the source code for the program (http://www.ohif.org; http://www.cornerstonejs.org). Overall, the platform has been downloaded more than 8,500 times, and has been translated into several languages.

Three examples of projects using the OHIF Viewer and/or its underlying Cornerstone libraries for COVID-19 imaging applications are:

From Australia, the DetectED-X CovED virtual clinical environment platform providing education on COVID-19 appearances on CT scans to radiologists worldwide;

From South Korea, the VUNO Med LungQuant and VUNO Med Chest X-ray artificial intelligence (AI) programs for diagnosis of COVID-19;

From Germany and Brazil, the Nextcloud DICOM Viewer - an open source, secure, fast, cloud-based, and simple web-based medical image viewer being used to diagnose COVID-19 from sites across Brazil, where it allows secure and fast diagnosis.

All of these applications are being provided for free to help support efforts to address this worldwide pandemic.

Meanwhile, the OHIF Viewer has become a mainstay for an elite set of cancer centers, through the Precision Imaging Metrics program developed at MGH and the Dana-Farber/Harvard Cancer Center. Users of this program perform over 25,000 oncology imaging assessments per year for over 1,000 active clinical trials with Precision Imaging Metrics. The NCI-designated Cancer Centers who are members and using this platform for clinical trials imaging informatics include:

Dana-Farber/Harvard Cancer Center

Yale Cancer Center

Fred Hutchinson Cancer Research Center at University of Washington

Huntsman Cancer Institute at University of Utah

Winship Cancer Institute at Emory University

Massey Cancer Center at Virginia Commonwealth University

Medical College of Wisconsin

Karmanos Cancer Center at Wayne State University

Nationwide Children's Hospital (launching 2020)

"Many academic and industry projects are also using the OHIF platform and associated Cornerstone tools for developing novel web-based imaging applications, and machine learning companies are now also tapping into it. We only hear about a fraction of the companies that are using it since it is free for anyone to download and customize. Hundreds of software developers around the world have adopted our platform and we welcome contributions from the user community," says Harris.

"Potentially inappropriate medications (PIMs)" are treatments that sometimes pose risks that outweigh their benefits, particularly for people who are 65 or older. About 20 to 60 percent of older adults take medicines that may be potentially inappropriate. That can increase the risk for being hospitalized, needing to visit the emergency department, having poor quality of life, and/or experiencing a harmful reaction.

When older adults are hospitalized for medical reasons or for surgery, they often go home with prescriptions for treatments that may be different from those they were taking beforehand. These treatments may include PIMs. Until now, however, few studies have examined how PIMs affect older adults when prescribed at the time of their hospital discharge.

A team of researchers recently designed a study to learn more about this important issue. They examined information from medical and surgical patients to evaluate the association of PIMs (both the ones the patients had been taking earlier as well as those newly prescribed at their hospital discharge) with the risk of four outcomes. The outcomes were harmful drug problems, emergency department visits, readmission to the hospital, and death after hospital discharge. The study was published in the Journal of the American Geriatrics Society.

This study was conducted in Quebec, Canada, where full information is available on all medical visits, emergency department visits, hospitalizations, and deaths. The researchers selected patients who were 65 years old or older and were discharged from one of the hospitals included in the study. When they were discharged, they were given prescriptions for one or more medications. Patients were followed until 30 days after their discharge or death, whichever came first.

Information from 2,402 patients was included in the study. Overall, patients were around 76 years old, had been diagnosed with five health conditions, and had been prescribed approximately eight different medications at the time of their discharge.

The researchers learned that 1,576 people--nearly two-thirds of all patients--had been prescribed at least one PIM at discharge. This included both new PIMs and/or those continued from before their hospitalization. Most patients were prescribed one PIM, and 1,176 patients were re-prescribed at least one of their previous PIMs. Nearly half of patients studied were prescribed with at least one new PIM.

Almost 10 percent of patients experienced a potentially harmful drug reaction and 36 percent visited the emergency department, were readmitted to the hospital, and/or died in the 30 days after their hospital discharge.

The researchers concluded that older adults who have been hospitalized and who are prescribed PIMs experience an increase in potentially harmful drug reactions, emergency room visits, rehospitalizations, and death within 30 days of discharge.

As people age, cancer becomes an increasing health concern. Solid cancer tumors are cancers that don't affect the blood and instead form tumors, or growths of abnormal cells in certain parts of the body. These solid cancer tumors mainly impact people who are 65 and older.

If you or an older loved one is diagnosed with cancer, many different factors come into play to guide treatment choices. However, leading geriatric oncologists (specialists who treat cancer in older adults) say that, perhaps surprisingly, age is not necessarily one of them. Recently, leaders in the field emphasized that being older, on its own, does not necessarily mean that surgical treatment is not an option for you.

Older patients with cancer may not receive the same treatment as younger adults. The reasons for this are unclear and may include the fact that surgical oncologists fear a higher risk of poor outcomes for older cancer patients following surgery. They may be uncertain about how surgery will affect an older patient's survival and quality of life. But since long-term outcomes after surgery for older adults with cancer have not been well-studied, we don't know whether such concerns are justified.

Fortunately, a screening tool exists that may help surgical oncologists and other physicians decide which patients might face complications after surgery. The "Preoperative Risk Estimation for Onco-Geriatric Patients" (or PREOP) risk score uses several easy-to-administer tests and can be given to people before surgery. The risk score includes a nutritional risk score to make sure you aren't malnourished and a test called Timed Get Up and Go (TUG). In this simple test, you are timed getting out of a chair, walking 10 feet, and sitting back down again.

In addition to these two tests, the PREOP risk score also takes into consideration your gender, how significant your surgery will be, and an anesthesiologist's assessment of your physical condition. In a previous study, a high PREOP risk score was found to be associated with an increased risk of major postoperative complications within 30 days after surgery.

A team of researchers recently examined how the PREOP score might predict how older adults fared following surgery for cancer. The researchers said they hoped their study would help both physicians and patients make decisions regarding cancer surgery. They published their study in the Journal of the American Geriatrics Society.

The researchers studied information from the PREOP study, designed by the surgical taskforce of the International Society of Geriatric Oncology (SIOG). The study was conducted on patients aged 70 or older who had surgery for suspected cancerous solid tumors. Medical centers that participated in the PREOP study collected additional information on survival for up to five years after a patient's surgery. They also wanted to learn more about whether the patients were independent or entered an assisted living facility or a nursing home within two years after surgery. The researchers in this new study examined information from 229 patients.

The patients in the study were followed for about 4.5 years after their surgery. Overall, the survival rate after surgery was:

84 percent survived 1 year after surgery

77 percent survived 2 years after surgery

56 percent survived 5 years after surgery

Of the patients who were alive one year after surgery, 43 (26 percent) moved to an assisted living facility or a nursing home, and by 2 years almost half of the entire study population (46 percent) moved to a care facility or had died. Survival at one year after surgery was worse for patients with a high PREOP risk score, compared with a normal PREOP risk score. However, the PREOP risk score could not predict whether patients were at an increased risk of needing to be cared for in a health facility or institution.

The researchers said that their study suggested that advancing age, on its own, should not be a reason for older adults to rule out surgery to cure or treat cancer. In fact, the researchers said they learned that survival rates were good and that most people were able to live independently at home even after surgery.

Still, the researchers noted that not all older patients with cancer will be able to return to the level of function they had before their surgery. They suggested that patients should have a detailed discussion with their doctors about the goals and expectations of surgery. The PREOP risk score can be used as a tool to guide this discussion.

Treatment of low-grade upper tract urothelial cancer usually involves radical surgery to remove the kidney and ureter, highlighting the need for improved treatments. An international team led by researchers at Baylor College of Medicine reports in the journal The Lancet Oncology that an innovative form of local chemotherapy using a mitomycin-containing reverse thermal gel offers a kidney-sparing treatment option for this rare cancer affecting 6,000 to 8,000 new patients in the United States every year.

"Urothelial cancer refers to a cancer of the lining of the urinary system. While about 9 of 10 urothelial cancers arise in the bladder (lower tract), a small subset arises in the upper tract, in the lining of the kidney or the ureter, the long, thin tube that connects that kidney to the bladder," said corresponding and senior author Dr. Seth P. Lerner, professor of urology and Beth and Dave Swalm Chair in Urologic Oncology at Baylor.

To spare patients having to undergo radical kidney surgery, physicians treated the cancer with a novel formulation of mitomycin, a form of chemotherapy that urologists use to treat low-grade cancers of the bladder. Standard formulations of mitomycin are administered in a water-based solution that is washed away by the urine produced by the kidney, shortening the time the drug is in direct contact with the urothelium, which lessens the effect of the treatment. To overcome the shortcomings of standard mitomycin treatment, Lerner and his colleagues evaluated a mitomycin-containing reverse thermal gel (UGN-101, brand name Jelmyto, manufactured by UroGen Pharma).

"UGN-101 is semi-solid at body temperature and becomes a viscous liquid at colder temperatures that can be injected via a catheter passed from the bladder into the renal pelvis where these tumors occur," Lerner said. "The reverse thermal properties of UGN-101 allow for local administration of mitomycin as a liquid, which subsequently transforms into a semi-solid gel depot as it warms up following instillation into the urinary upper tract. Normal urine flow dissolves the gel depot, allowing tissue exposure to mitomycin over a period of 4 to 6 hours."

The researchers previously reported proof-of-concept and preliminary safety data for UGN-101 in treating 22 patients with upper tract urothelial cancer in a compassionate-use program. In the current study, Lerner and his colleagues conducted a phase 3 single-arm clinical trial to further evaluate the efficacy of the innovative reverse gel delivery of mitomycin in low-grade upper tract urothelial cancer.

Seventy-one patients received six weekly treatments with mitomycin-containing reverse thermal gel. Patients who had a complete response (complete disappearance of the tumor) were offered monthly treatments for up to 11 additional months. Efficacy of the treatment was evaluated using urine cytology (a test to look for abnormal cells in a patient's urine), ureteroscopy (an examination of the upper urinary tract) and biopsy (if warranted) three months following the initiation of therapy.

The treatment was beneficial. Following the initial six weekly treatments, 59 percent of the patients had no residual tumors, including patients with cancer deemed unresectable at diagnosis, who represented 48 percent of the overall treatment population. There were side effects, including urinary tract infection, hematuria (blood in urine), flank pain and nausea, but the severity and frequency were as expected from patients who are undergoing similar interventions. The study will continue to monitor the durability of the initial response out to 12 months.

The treatment has been recently approved by the U.S. Food and Drug Administration and became the first and only approved non-surgical treatment available for patients with low-grade upper tract urothelial cancer.

"The clear benefit is that patients get to keep their kidney. For people who have one kidney, this option also removes the need for dialysis," Lerner said. "Other potential beneficiaries would be patients for whom, because of other conditions, it would be too risky to perform an operation to remove the kidney. Now they have an option for treatment."