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Is artificial intelligence the key to preventing relapse of severe mental illness?

New AI software developed by researchers at Flinders University shows promise for enabling timely support ahead of relapse in patients with severe mental illness.

The AI2 (Actionable Intime Insights) software, developed by a team of digital health researchers at Flinders University, has undergone an eight-month trial with psychiatric patients from the Inner North Community Health Service, located in Gawler, South Australia.

The digital tool is tipped to revolutionise consumer-centric timely mental health treatment provision outside hospital, with researchers labelling it as readily available and scalable.

In the trial of 304 patients, the AI2 software found that 10% of them were at increased risk of not adhering to treatment plans by failing to take medication or disengaging with health services.

This led to interventions which clinicians believe could have prevented the patient from relapsing and experiencing a deterioration of their mental health.

The web-based tool uses algorithms to automatically flag gaps in care interactions between different parts of the health system.

The project is led by Flinders' Associate Professor Niranjan Bidargaddi who says that the current monitoring, management, and treatment of chronic mental illness across different parts of the health system is poorly coordinated and inadequate.

"In Australia there are about 600,000 people living with a chronic mental illness with multiple morbidities" he says.

"One a patient has sought an initial consultation with a clinician they might be provided with a diagnosis, a mental health care plan and then they are sent off with instructions for treatment such as taking medication or trying therapeutic techniques. Multiple ongoing medical appointments and medications are burdensome for patients to manage on their own.

"The problem is that most clinicians don't have the resources to keep track of every patient manually. This can lead to the patient relapsing and potentially becoming hospitalised."

Some estimates suggest that more than 80% of patients with severe mental illness will relapse several times within the firth five years of their initial treatment.

Patients can relapse for a variety of reasons. They might experience intolerable side effects or little initial benefit from the medication, have a poor understanding of the need for ongoing treatment or suffer circumstances such as forgetfulness or homelessness.

"This puts the patient on a downhill trajectory, can cause a worsening of symptoms and have an increased burden on the public health system," A/P Bidargaddi says.

"AI2 delivers important data in real time, providing clinicians with an effective digital alternative to monitoring patients."

Patients included in the study had diagnoses of schizophrenia, schizo-affective disorder, bipolar or other mood disorders and had been prescribed ongoing psychotropic medications.

If taken properly, antipsychotic, antidepressant and mood stabilising medications are highly effective in reducing the risk of relapse of severe mental illness.

The AI2 software continuously analyses a clinician's consented patients' Medicare Benefit Scheme (MBS) and Pharmaceutical Benefits Scheme (PBS) data, such as medication prescriptions, from the national My Health Records.

Algorithms running on the cloud monitor the patients' data to detect gaps in continuity of care such as medical appointments attendance, prescription refills, or mental health care plan review.

Once the gaps are detected, it triggers an intervention alert with the monitoring clinician, prompting them to intervene.

A/P Bidargaddi says the study found that monitoring the AI dashboard is not onerous.

"The two clinician monitors spend about two hours per week monitoring the dashboard, reviewing case notes and speaking with case managers," he says.

"Feedback from the clinicians at this stage suggests they actually saved time on routine calls, as they would only contact the GP when necessary - such as if the software had detected a missed prescription refill."

While the rollout of AI2 is currently limited to SA, A/P Bidargaddi says the next step for AI2 is for a randomised controlled trial to be carried out across multiple sites.

This will determine whether the technology leads to a reduction in hospitalisation over time, and whether it's cost effective.

A/P Bidargaddi is working with Digital Health CRC to further refine the quality of algorithms further and explore its use in facilitating optimal care interactions for other chronic conditions such as diabetes.

Certain patients with an aggressive form of ovarian cancer have a better chance of a cure through surgical removal of their tumor before chemotherapy instead of the reverse, a new study shows.

Led by researchers at NYU Grossman School of Medicine, Perlmutter Cancer Center, and Dana-Farber Cancer Institute, the study used a mathematical tool to examine how doctors should coordinate available treatments for high-grade serous ovarian cancer (HGSC).

Ovarian cancer is the 8th most common cancer and cancer death in women worldwide, and HGSC constitutes roughly 70 percent of ovarian malignancies and has the worst prognosis. Patients with the condition typically undergo surgery and chemotherapy, but there has been long-standing controversy over the best order of treatment.

Published online June 14 in Proceedings of the National Academy of Sciences, the new analysis argues that patients who can undergo "complete debulking" surgery first, with chemotherapy added after (termed primary debulking surgery or PDS), should have a superior outcome to the other main treatment option: giving patients a few cycles of chemotherapy to shrink the tumor before surgery (neoadjuvant chemotherapy or NACT).

"The issue of whether PDS or NACT should be used was highly controversial, and a major reason for it lies in the different characteristics of patients in different clinical studies," says study first author Shengqing Gu, PhD, a graduate from University of Toronto and now an instructor at Dana-Farber Cancer Institute. "We therefore built a mathematical model to simulate HGSC clinical course, which allows us to compare treatment outcomes in the same virtual patients and examine which group of patients may respond differently to PDS vs NACT."

"Our model, combined with earlier clinical data, suggests that for patients who can undergo complete debulking, surgery offers the best chance of long term survival or even cure," says study co-senior author Benjamin G. Neel, MD, PhD, director of Perlmutter Cancer Center at NYU Langone Health. "Our model also provides some insight about optimal early detection and treatment intervals."

The researchers used clinical data from roughly 300 patients in previous studies of patients' responses to PDS or NACT, taken from the Princess Margaret Cancer Center in Toronto and the Canadian Cancer Trials Group.

The researchers found that in patients who are well enough for surgery, debulking provides better results because it has the best chance of removing cancer cells resistant to chemotherapy. For patients who are too ill for debulking surgery, the study suggests that a shorter period of initial chemotherapy, rather than the currently recommended interval, might provide a greater benefit.

The current analyses suggest several questions that future randomized clinical trials should examine, say the study authors. These include how much the influence of the time gap between surgery and subsequent chemotherapy may affect treatment outcome, whether there is a link between the number of initial chemotherapy cycles and outcomes, and whether complete secondary surgery on relapsed tumor improves prognosis.

"Our model shows that a fraction of patients can have long term survival or even cure, but only when they undergo complete debulking, followed by the currently available therapies," Neel says. "There is an urgent need for new therapies to provide cures for patients for whom complete debulking is not an option and for those with the most treatment-resistant cancer cells."

What The Study Did: The results suggest assisted living residents experienced increased mortality during the COVID-19 pandemic consistent with increases observed among nursing home residents.

Authors: Kali S. Thomas, Ph.D., of Brown University in Providence, Rhode Island, 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/jamanetworkopen.2021.13411)

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

A non-contact laser imaging system could help doctors diagnose and treat eye diseases that cause blindness much earlier than is now possible.

The new technology, developed by engineering researchers at the University of Waterloo, is designed to detect telltale signs of major blinding diseases in retinal blood and tissue that typically go unseen until it is too late.

With current testing methods, diseases such as age-related macular degeneration, diabetic retinopathy and glaucoma--which have no symptoms in their early stages--are usually diagnosed only after vision is irreversibly affected.

"We're optimistic that our technology, by providing functional details of the eye such as oxygen saturation and oxygen metabolism, may be able to play a critical role in early diagnosis and management of these blinding diseases," said Parsin Haji Reza, director of the PhotoMedicine Labs at Waterloo.

Patented technology at the core of the new system is known as photoacoustic remote sensing (PARS). It uses multicoloured lasers to almost instantly image human tissue without touching it.

When used for eyes, the non-invasive, non-contact approach dramatically improves both patient comfort and the accuracy of test results.

The technology is also being applied by Haji Reza and researchers in his lab to provide microscopic analyses of breast, gastroenterological, skin and other cancerous tissues, and to enable real-time imaging to guide surgeons during the removal of brain tumors.

"PARS may move us beyond the current gold standard in ophthalmological imaging," said Dr. Richard Weinstein, an ophthalmologist and co-founder of the Ocular Health Centre. "For the first time, not just in ophthalmology but in the entire medical field, diagnosis and treatment of disease could be made prior to structural change and functional loss."

Haji Reza, a professor of systems design engineering and co-founder of startup company illumiSonics, said researchers are working with several ophthalmologists and hope to start clinical trials within two years.

A paper on the research, Functional and structural ophthalmic imaging using noncontact multimodal photoacoustic remote sensing microscopy and optical coherence tomography, appears in the journal Scientific Reports.

The research team includes graduate students Zohreh Hosseinaee, Nicholas Pellegrino, Layla Khalili and Lyazzat Mukhangaliyeva, and research assistant Nima Abbassi.

The National Pharmaceutical Regulatory Agency (NPRA) of Malaysia has granted a conditional registration for a safe, effective hepatitis C treatment developed by a public-private partnership bringing together the Malaysian Ministry of Health, not-for-profit research and development organization Drugs for Neglected Diseases initiative (DNDi), Egyptian pharmaceutical company Pharco, Malaysian pharmaceutical company Pharmaniaga Berhad, and non-governmental-organization Médecins Sans Frontières/Doctors Without Borders (MSF).

This is the very first drug for hepatitis C virus (HCV) to be developed through South-South collaboration and with funding and clinical support from non-profit organizations.

This partnership was formed to address one of the more intractable public health challenges of the past decade: the lack of access to affordable direct-acting antivirals (DAAs), a newer generation of powerful HCV treatments that can cure patients in three to six months. HCV, which can lead to chronic liver disease, cirrhosis, cancer, and death, affects about 58 million people worldwide, but only about 13% have received treatment to date. The disease causes around 300,000 deaths a year.

'Although hepatitis can be cured, there is a vicious circle that stands in the way of providing treatment to all in need: the disease is mostly a 'silent killer', the diagnostic process is complex, so people go unfound, and DAAs are often too expensive,' said Tan Sri Dato' Seri Dr Noor Hisham Abdullah, Director General of Health, Ministry of Health, Malaysia. 'Malaysia decided to act to break this vicious circle. We are actively screening to find 'missing' patients, rolling out simpler diagnostic tests, and ensuring we have access to the best prices for treatments, including by conducting clinical research to identify additional affordable treatment options. Today's announcement is a milestone on Malaysia's long journey to achieve the World Health Organization goal of eliminating hepatitis C by 2030.'

The approval today concerns a new drug, ravidasvir, for the treatment of chronic HCV infection in adults in combination with other medicinal products. Ravidasvir was developed by the partnership for use with sofosbuvir, an existing DAA, as an affordable, simple, and efficacious public health tool.

DNDi and partners conducted STORM-C-1, an open-label clinical trial to assess the efficacy, safety, and pharmacokinetics of ravidasvir combined with sofosbuvir in Malaysia and Thailand. The study was sponsored by the Ministries of Health of Malaysia and Thailand, and DNDi. In results published in April 2021 in The Lancet Gastroenterology & Hepatology, the combination showed cure rates of 97% and was well tolerated in a diverse adult population with chronic HCV infection. This included people infected with genotype 3 of the virus, which is particularly hard to treat. No clinically significant drug-drug interactions with the antiretrovirals commonly used to treat HIV were found, which will make this new combination particularly useful to clinicians.

'The development of this new drug is the result of a partnership between public and private actors sharing the same public health objective from the very start: the development of an affordable medicine. It is a concrete example of how research and development can deliver innovation driven by public health needs, rather than market imperatives,' said Dr Bernard Pécoul, Executive Director of DNDi.

Ravidasvir is an oral NS5A inhibitor discovered and owned by Presidio Pharmaceuticals. It was licensed to Egyptian drug manufacturer Pharco Pharmaceuticals and DNDi for clinical development and commercialization. In an earlier Phase III clinical trial in Egypt conducted by Pharco, ravidasvir + sofosbuvir showed cure rates of up to 100% in patients with genotype 4. Pharco and DNDi partnered with Malaysian drug manufacturer Pharmaniaga for the registration and supply of ravidasvir in Malaysia and South-East Asia.

'This new treatment will be a powerful tool in our arsenal to make the vision of a hepatitis C-free world a reality,' said Dr Sherine Helmy, CEO of Pharco Pharmaceuticals. 'This is why this new combination will be sold at an affordable price between USD 300-500 for a 12-week treatment course.'

'NPRA approval is a huge milestone for all parties who have been working tirelessly to make a safe, effective, accessible and, most importantly, affordable treatment for hepatitis C in Malaysia,' said Datuk Zulkarnain Mohamed Eusope, Pharmaniaga Group Managing Director. 'This is a first for us at Pharmaniaga, a generics company, being involved in the development of a new chemical entity. We thank the NPRA for their continuous support, and for prioritizing the approval, obtained within 15 months, compared to standard timelines of two years or more. We hope this latest development will increase options and facilitate access for the public to obtain a more affordable treatment for HCV.'

The STORM-C project was financed by MSF's Transformational Investment Capacity initiative, with the objective of increasing access to treatment for HCV patients in low- and middle-income countries.

'Hundreds of thousands of people die each year from the consequences of hepatitis C and expanding the access to cure is a medical humanitarian imperative,' said Pierre Mendiharat, Deputy Operations Director for MSF. 'HCV affects vulnerable and often marginalized populations including people who use drugs and people co-infected with HIV. To eliminate HCV, we need easy-to-use, simple, and affordable treatments that work, like the ravidasvir + sofosbuvir combination.'

Plans to register the new ravidasvir + sofosbuvir combination are advancing in other countries, including in Latin America.

'Our goal is now to help foster the political will and financing needed for wide-scale roll-out of lifesaving testing and treatment for hepatitis C globally,' said Dr Bernard Pécoul. 'The Malaysian example is a showcase of what can be done with the right will, the right partners, and the right tools.'

Niigata, Japan - Biomarkers are important determinants of appropriate and effective therapeutic approaches for various diseases including cancer. There is ample evidence pointing toward the significance of immune check point inhibitors (ICI) against cancer, and they showed promising clinical benefits to a specific group of patients with colorectal cancer (CRC). Several reports demonstrated the efficacy of biomarkers such as programmed death-1 protein ligand (PD-L1), density of tumor-infiltrating lymphocytes (TILs), and tumor mutational burden (TMB), to determine the patient responsiveness for the efficient use of ICIs as therapeutics against cancer.

A high level of TMB (TMB-H), which reflects elevated total number of non-synonymous somatic mutations per coding area of a tumor genome and normally derived from gene panel testing, is recognized as a promising biomarker for the ICI therapies of various solid cancers. However, in clinical practice, it is not feasible to perform gene panel testing for all cancer patients.

Dr. Yoshifumi Shimada and coworkers from the Division of Digestive and General Surgery, Graduate School of Medical and Dental Sciences, Niigata University, regarded TMB-H from a specific CRC patient subgroup, as a more robust marker for predicting the efficacy of ICIs, and developed a convolutional neural network (CNN) - based algorithm to predict TMB-H CRC directly from the histopathological characteristics, in particular, the TIL, obtained from the hematoxylin and eosin (H&E) stained slides. A representative microscopic image of the H&E stained tumor mutational burden-high colorectal cancer tumor is shown in the accompanying figure, demonstrating the presence of tumor-infiltrating lymphocytes in significantly elevated level compared to normal surrounding tissue. Digital information from such this neoplastic and also non-neoplastic images obtained from JP-CRC-cohort is transformed and normalized for building a predictive Convoluted Neural Network model employing Inception V3 learning model, by Dr. Shimada group. The CNN-based model developed by Dr. Shimada and coworkers has the potential to not only reduce the burden of proper diagnosis on pathologists but also provide the necessary information on the patients' responsiveness to the ICI based therapeutics, without the use of expensive, time consuming and not easily available gene panel testing. This study by Dr. Shimada and coworkers is published in a recent issue of Journal of Gastroenterology (2021; vol. 56: pp. 547-559; https://doi.org/10.1007/s00535-021-01789-w).

In addition, the studies of Dr. Shimada group also provided means to predict TMB-H CRC only by using the TIL information from the H&E slides from the patients' tumor tissues. However, considering that the patients in the studied cohort were not treated with any ICIs, no conclusions could be drawn regarding their ICI responsiveness following the TMB-H diagnosis and it was suggested that future clinical trials need to be conducted to address whether TIL alone can be useful as a predictive biomarker for the efficacy of ICIs. Dr. Shimada says about the present study: "We have developed artificial intelligence to predict genetic alterations in colorectal cancer by deep learning using hematoxylin and eosin slides. This artificial intelligence is important in solving the cost problems associated with genetic analysis and facilitating personalized medicine in colorectal cancer."

Overall, the studies by Dr. Shimada and associates provide a cost and time effective and reliable method to inform the clinicians if the CRC patient they are managing can benefit from Immune Checkpoint Inhibitor (including inhibitors of the PD-1 protein and its ligand, PD-L1) therapy, without implicating the use of gene panel.

BOSTON - Bronchiolitis--the most common lung infection in young children, and which is most often caused by respiratory syncytial virus, or RSV--is the leading cause of hospitalizations in U.S. infants, and about 30% of those with severe bronchiolitis later develop asthma. A team led by investigators at Massachusetts General Hospital (MGH) has uncovered four distinct molecular subtypes of RSV bronchiolitis and has linked a certain subtype to a higher asthma risk. The findings are published in Nature Communications.

"While bronchiolitis has been considered a single disease with similar mechanisms, emerging evidence has suggested that bronchiolitis consists of multiple disease subgroups," says lead author Yoshihiko Raita, MD, MMSc, a researcher in the MGH Department of Emergency Medicine. "But our limited understanding of RSV bronchiolitis, and how it varies, has held up efforts to develop RSV bronchiolitis treatment and asthma prevention strategies."

To provide insights, Raita and his colleagues analyzed diverse clinical, genetic and molecular data from 221 infants hospitalized with RSV bronchiolitis who were followed until five years of age. The scientists gathered information on the viruses that had infected the children, as well as information on the microbes, metabolites and immune response-related molecules present in the children's nasal passages.

Based on their analyses, four biologically and clinically meaningful subtypes, or endotypes, of RSV bronchiolitis exist. Of these, one endotype--which is characterized by coinfection by rhinovirus, dominance by specific bacteria, and high interferon (antiviral) response--had an approximate 40% risk of developing asthma by age five.

"Our data add significant support to the emerging concept that bronchiolitis represents several diseases with unique biological mechanisms," says Raita. "For clinicians, our findings give an evidence base for the early identification of high-risk children during an important period of airway development: early infancy. For researchers, our data offer new avenues for the development of subgroup-specific strategies--such as fine-tuning the airway immune response and microbiome--for treating bronchiolitis and preventing asthma."

These are the findings of an Imperial-led study using data from thousands of children in England over a number of years, which looked at the health impact of consuming ultra-processed foods (UPFs) - food and drink heavily processed during their making, such as frozen pizzas, fizzy drinks, mass-produced packaged bread and some ready meals.

Researchers found that not only do UPFs make up a considerably high proportion of children's diets (more than 40% of intake in grams and more than 60% of calories on average), but that the higher the proportion of UPFs they consume, the greater the risk of becoming overweight or obese.

In addition, they highlight that eating patterns established in childhood extend into adulthood, potentially setting children on a lifelong trajectory for obesity and a range of negative physical and mental health outcomes including diabetes and cancers.

The authors explain the research, published today in the journal JAMA Pediatrics, provides important evidence of the potential damage of consuming highly processed foods which are often cheap, widely available and highly marketed. They say that action is needed urgently to reduce UPF consumption among children.

Professor Christopher Millett, NIHR Professor of Public Health at Imperial College London, said: "We often ask why obesity rates are so high among British children and this study provides a window into this. Our findings show that an exceptionally high proportion of their diet is made up of ultra-processed foods, with one in five children consuming 78% of their calories from ultra-processed foods.

"Through a lack of regulation, and enabling the low cost and ready availability of these foods, we are damaging our children's long-term health. We urgently need effective policy change to redress the balance, to protect the health of children and reduce the proportion of these foods in their diet."

Dr Eszter Vamos, Senior Clinical Lecturer in Public Health Medicine at Imperial, said: "One of the key things we uncover here is a dose-response relationship. This means that it's not only the children who eat the most ultra-processed foods have the worst weight gain, but also the more they eat, the worse this gets."

"Childhood is a critical time when food preferences and eating habits are formed with long-lasting effects on health. We know that if children have an unhealthy weight early in life, this tends to trace into adolescence and then adulthood. We also know that an excessive consumption of ultra-processed foods is linked to a number of health issues including being overweight or obese, high blood pressure, cardiovascular disease, type two diabetes and cancer later in life, so the implications are enormous."

This latest study provides new, important data on the impact of industrial food processing, in which foods are modified to change their consistency, taste, colour, shelf life or other attributes through mechanical or chemical alteration - typically lacking in traditional, home-prepared meals - on child health.

Led by a team from Imperial's School of Public Health, the work is the first to look at the link between the consumption of UPFs and obesity in children over a long period of time, with findings broadly applicable to children across the UK.

Using data from a cohort of 9,000 children in the Avon area in the West of England born in the early 1990s, researchers were able to follow the life course of children from the age of 7 until the age of 24. As part of this cohort, food diaries were completed at age 7, 10 and 13, recording the food and beverages children consumed over three days. Data measures were also collected over 17 years, covering areas including body mass index (BMI), weight, waist circumference and measurements of body fat.

Researchers categorised children into five equally-sized groups based on the consumption of UPFs in their diet - in the lowest group UPFs accounted for one fifth (23.2% of grams) of total diet, while the highest group consumed more than two-thirds of UPFs (67.8% of grams). Major sources of UPFs in the highest consumption group included fruit-based or fizzy drinks, ready meals, and mass-produced packaged bread and cakes. Comparatively, diets in the lowest consumption group were based on minimally processed foods and beverages, such as plain yogurt, water and fruit.

The analysis revealed that on average, children in the higher consumption groups saw a more rapid progression of their BMI, weight, waist circumference and body fat into adolescence and early adulthood. By 24 years of age, those in the highest UPF group had, on average, a higher level of BMI by 1.2 kg/m2, body fat by 1.5%, weight by 3.7 kg and waist circumference by 3.1 cm.

Kiara Chang, Research Fellow and first author on the paper, said: "During the 17 years of follow up, we saw a very consistent increase in all measures of unhealthy weight among children who consumed greater amounts of ultra-processed foods as part of their diet. Their BMI, weight gain, and body fat gain was much quicker than those children consuming less ultra-processed foods. We actually see it making a difference from as young as 9 years old, between those consuming the most compared with those consuming the least ultra-processed foods."

The researchers highlight that a limitation of the study is its observational nature, and that they are unable to definitively show direct causation between consumption of UPFs and increases in BMI and body fat.

According to the researchers, more radical and effective public health actions are needed urgently to reduce children's exposure and consumption of UPFs and to address childhood obesity in the UK and internationally. These actions should include:

National dietary guidelines should be updated to emphasise preference for fresh or minimally processed foods and avoidance of ultra-processed foods, in line with guidelines developed in Brazil, Uruguay, France, Belgium and Israel.

UPFs should be taxed and minimally processed foods should be subsidised to make healthier food choices more affordable. Other actions include restricting promotions and all forms of advertising of UPFs, especially those targeting children, and mandatory bold front-of-pack product labelling.

They add that further studies are now needed to determine the underlying mechanisms linking UPF consumption to worse health outcomes. Hypotheses include that UPFs produce lower satiety, meaning that people do not feel full after eating these products, encouraging excess consumption. More research is also needed to explore whether additives in highly processed food interfere with biological processes, such as hormones influencing appetite and glucose control.

Professor Millett featured in the recent BBC One documentary 'What Are We Feeding Our Kids?', in which he said: "Today in Britain, two in every three calories consumed amongst children and adolescents is derived from this group [of ultra-processed foods]. They're everywhere, they're cheap, and they're heavily marketed. So they're very difficult to resist and very difficult to avoid."

Boston - Hypertension, or high blood pressure, kills more Americans than any other health condition. It is especially prevalent in Black Americans and is exacerbated by structural barriers to accessing high quality healthcare. In a 2018 randomized trial called the Los Angeles Barbershop Blood Pressure Study (LABBS), barbers were trained to screen their Black male patrons for hypertension and refer them to a pharmacist who visited the barbershop to counsel and treat individuals with high blood pressure. Participants in the barbershop-based, pharmacist-led program saw a 20-point drop in systolic (top number) blood pressure that they were able to sustain beyond the duration of the trial.

In a new paper published in the journal Circulation, researchers built a model to examine the potential impact of implementing similar blood pressure control programs at barbershops nationwide. The team found that such programs could reach one in three Black men with uncontrolled blood pressure nationally. Among men who participate, the program could avert 40 percent of major cardiovascular events like heart attacks or stroke.

The team also examined the economic constraints under which the program would have to be implemented in order to be considered cost-effective, and estimated that if barbershop-based programs could be delivered at a cost of roughly $1,500 per enrolled participant per year, it would be considered cost-effective by U.S. standards.

"Barbershop-based, pharmacist-led blood pressure control programs represent a novel and effective way to deliver hypertension care to Black men, who represent an underserved population that is disproportionately affected by the complications of uncontrolled hypertension," said lead author Dhruv S. Kazi, MD, MS, Associate Director of the Richard A. and Susan F. Smith Center for Outcomes Research in Cardiology at Beth Israel Deaconess Medical Center (BIDMC). "Our findings provide a blueprint to guide nationwide implementation of a program that has the potential to save lives and improve health outcomes at a reasonable cost per participant."

Kazi and colleagues projected clinical outcomes and direct healthcare costs of implementing barbershop-based, pharmacist-led blood pressure control programs, relative to usual care over 10 years. The team based these projections on the likely clinical outcomes for a hypothetical cohort of Black men ages 35-79 years living in U.S. metropolitan areas with a systolic (top number) blood pressure of 140 or above. Assuming the programs could reduce mean systolic blood pressure by 20 points, as was achieved in the LABBPS program, these community-based interventions would avert 8,600 major cardiovascular events annually relative to usual care, including 1,800 myocardial infarctions, or heart attacks, and 5,500 strokes. This is projected to lower healthcare costs by more than $200 million dollars a year.

Despite a range of pre-existing programs and incentives, blood pressure control in the U.S. has worsened in recent years. "There is no reason for us to accept the status quo - there are plenty of effective and affordable medications for blood pressure control if we can address the structural barriers to getting them to people," said Kazi, who is also Associate Professor at Harvard Medical School. "The barbershop-based blood pressure control program, pioneered by the late Ronald G Victor, MD, challenges the dogma that high-quality blood pressure control can only happen in healthcare settings. By changing the locus of care to a trusted community setting and allowing trained pharmacists to prescribe antihypertensives and escalate doses of medications, Dr. Victor's program achieved really impressive declines in blood pressure in an underserved population."

Kazi concluded that to improve the health and lives of diverse communities, experts need to learn how to translate the findings of successful clinical trials into large-scale, cost-effective programs using tools from health economics and implementation science. "Our analysis advances that conversation by showing the way forward, clarifying how these programs can be scaled nationally and quantifying the enormous potential health benefits such a scale-up would bring."

(Boston)-- The concept of rationing medical resources during the height of COVID-19 pandemic created tremendous anxiety in the patient and healthcare communities. In planning for that possibility Massachusetts created a triage scoring system focusing on an acute survival score that considers chronic life-limiting medical conditions of the patient, but it does not provide specifics about how to value those conditions in the equation.

Now a new study supports prioritizing resources to those who are most likely to survive an acute illness as several chronic medical conditions had less of an impact on longer-term survival than previously suspected.

"No one ever wants to use a triage system to ration ventilators, leading some people to die from lack of ability to provide care. However, in the event of such a crisis, like the COVID-19 pandemic, the public needs to be confident that those who are prioritized to receive a ventilator for example, have a higher likelihood of survival," explained corresponding author Anna Cervantes-Arslanian, MD, assistant professor of neurology at Boston University School of Medicine.

The researchers obtained the hospital records of all patients admitted to an Intensive Care Unit at Boston Medical Center (BMC) in the first 15 days of April in 2015 and 2019 and applied the scoring system the hospital developed for prioritizing patients during the first wave of the COVID-19 pandemic. Patients with chronic medical conditions (kidney failure on dialysis, cirrhosis, chronic lung disease, congestive heart failure, dementia, metastatic cancer) were given a score associated with their likelihood of dying in one and five years. They then assessed in 2016 and 2020 whether patients indeed were alive or dead.

What they discovered was that there was a lot of variability amongst "chronic medical conditions" with the criteria for some illnesses being better than others at predicting death. Certain patients with conditions which they thought would be associated with a high mortality at one and five years were actually alive. The researchers also note that a very small number of patients actually met the criteria being used to triage resources, thus providing a strong reason to eliminate or decrease importance of chronic medical conditions in the scoring.

"The public has a right to understand the specifics of how medical resources are utilized/triaged and whether the system to determine utilization is based upon scientific evidence versus assumptions. Our findings support weighing acute survival as much more important than chronic medical conditions because in some cases, we were not good at identifying populations with high mortality," added Cervantes-Arslanian, who is also director of neurocritical care at BMC.

These findings appear online in the journal Critical Care Medicine.

(Boston)--Despite evidence regarding the benefits of vaginal birth after cesarean and recommendations to support shared decision making to reduce cesarean rates, minority women face many impediments that limit their access to appropriate health information and opportunities for such discussions.

Haitian women in Massachusetts have the highest rates of cesarean section and low rates of vaginal birth after cesarean, despite evidence suggesting that many are eligible to attempt vaginal birth after a previous cesarean.

Now a new study explores how Haitian women's beliefs, values and attitudes influence their decision making about pregnancy and birth after having had a cesarean delivery. In conjunction with the providers' views about Haitian women, the information learned was used to develop a group counseling curriculum to enhance shared decision making between the women and their care provider.

"Given the low rates of vaginal birth after cesarean in many non-English speaking groups within the U.S., it is vital to find ways to ensure that these groups have access to respectful maternity care and the recommended shared decision making discussions about mode of birth after cesarean," says corresponding author Somphit Chinkam, CNM MPH, DNP, clinical assistant professor of obstetrics and gynecology at Boston University School of Medicine.

In an effort to understand a Haitian woman's unique perspectives and needs, focus groups for them and their prenatal providers were held. The Haitian women discussed where they obtained pregnancy and birth-related information; how counseling about the modes of birth options was given by their prenatal provider; whether they felt comfortable asking questions; how they planned to give birth (planned cesarean or vaginal birth) for this pregnancy; and any type of support they used to make their mode of birth decision.

Four themes were found to provide an improved understanding about the influences on both groups: Haitian culture; paucity of information; importance of family, friends and providers; and fear of pain during either mode of birth. "Being mindful of these four themes allows providers caring for Haitian Creole-speaking women to tailor their counseling and care to ensure the highest level of shared decision-making regarding mode of birth counseling," added Chinkam, a certified midwife at Boston Medical Center.

These findings appear online in the Journal of Health Care for the Poor and Underserved.

Fully occupied intensive care units (ICUs). Physically and mentally exhausted health workers. Chaotically overcrowded hospitals. These and similar problems posed by the COVID-19 pandemic in Brazil have created ideal conditions for the emergence of Candida auris, a microorganism some are calling a "superfungus" because of the speed with which it has developed drug resistance.

The first two cases were confirmed in December 2020 at a hospital in Salvador (state of Bahia, Northeast Brazil), and are described in the Journal of Fungi by a group of researchers led by Arnaldo Colombo, head of the Special Mycology Laboratory at the Federal University of São Paulo (UNIFESP). The study was supported by São Paulo Research Foundation - FAPESP.

"Nine other C. auris patients have since been diagnosed at the same hospital, some colonized [with the fungus in their organism but not doing harm] and others infected," Colombo told. "No other cases have been reported in Brazil, but there are grounds for concern. We're monitoring the evolutionary characteristics of C. auris isolates from patients at the hospital in Salvador, and we've already found samples with reduced sensitivity to fluconazole and echinocandins. The latter belong to the main class of drugs used to treat invasive candidiasis."

Except for C. auris, fungi of the genus Candida are part of the human gut microbiota and cause problems only when there are imbalances in the organism, Colombo explained. These include infections such as vaginal yeast infection and thrush (oral candidiasis), often caused by C. albicans.

In some cases, however, the fungus enters the bloodstream and causes a systemic infection known as candidemia, the most common form of invasive candidiasis, similar to bacterial sepsis. Invasion of the bloodstream and the immune system's exacerbated response to the pathogen can cause damage to several organs and even lead to death. According to scientific evidence, mortality among candidemia patients infected by C. auris can reach 60%.

"The species quickly becomes resistant to multiple drugs and isn't very sensitive to the disinfectants used by hospitals and clinics," Colombo said. "As a result, it's able to persist in hospitals, where it colonizes health workers and ends up infecting patients with severe COVID-19 and other long-stay critical patients."

Several factors make patients infected by SARS-CoV-2 ideal targets for C. auris, including long hospital stays, urinary and central venous catheters (allowing invasion of the bloodstream), and steroids and antibiotics (which disrupt the gut microbiota).

"The virus can damage the intestinal mucosa of severe COVID-19 patients [facilitating invasion of the bloodstream by pathogens] so that the patient becomes vulnerable to candidemia," Colombo said.

Several countries have reported the emergence of C. auris during the COVID-19 pandemic, he added, making the need to intensify control of hospital-acquired infections throughout Brazil even more urgent. Rational use of antimicrobial drugs in ICUs is equally important. Since the start of the pandemic, azithromycin and other antibiotics have been more widely prescribed, mostly without a genuine justification.

Monitoring

C. auris was first isolated in Japan in 2009 but the scientific community paid it little attention until some years later when outbreaks of candidemia caused by the superfungus occurred in Asia and Europe. In 2016, an article by the UNIFESP group in the Journal of Infection reported the arrival of the species in the Americas via Venezuela. It was soon detected in Colombia, Panama and Chile.

"In 2017 we participated in a task force convened by the Health Ministry and ANVISA [Brazil's health surveillance authority] and wrote a technical standard [Risk Notice 01/2017] warning health services that precautionary measures should be taken to monitor the possible arrival of C. auris in Brazil, which was confirmed only at the end of last year," Colombo said.

Since then, the UNIFESP team has been monitoring the emergence of novel fungal pathogens in bloodstream infections documented by medical centers across Brazil, without detecting C. auris until now.

Five clades or lineages of C. auris have so far been described in the world. According to Colombo, the clade isolated in Salvador resembles the Asian original more closely than the variant detected in Venezuela and other South American countries, suggesting a second independent arrival of the superfungus on the continent.

"Alternatively, there may be a local environmental source, since none of the Brazilian patients infected by the fungus traveled abroad or had infected relatives," Colombo said.

Every month since December, the researchers have received samples of the clade isolated at the hospital in Salvador for testing of its sensitivity to antifungal drugs in their laboratory.

"In these tests, we expose the cultured microorganism to progressive concentrations of antifungals in order to determine the lowest dose that can inactivate it. In the case of C. auris present in samples recently isolated in Salvador, for example, the dose has to be four to five times larger than the dose used to inactivate the isolate cultured in December 2020," Colombo said.

In partnership with Dutch colleagues, the UNIFESP group is conducting a genetic sequencing study to see if the gene that confers drug resistance on C. auris has mutated during the period.

"The mechanism that enables the species to develop drug resistance isn't enzymatic degradation, as in so many bacteria that are resistant to antibiotics," Colombo said. "The fungus develops structural modifications in the proteins to which the drug binds to inhibit cell wall synthesis [glucan synthase in the case of echinocandins], which is key to its survival. We're seeing this phenomenon happen here in Brazil."

In addition to redoubled care with hygiene, surveillance efforts to detect suspected pathogens should be stepped up, he added. Confirming the presence of C. auris in a sample is no trivial task, requiring specific equipment. The most widely used technique is matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, fairly commonplace in microbiology laboratories but not always available in hospitals in Brazil.

"If the analysis is conducted using conventional automated methods, C. auris can be confused with other species, such as C. haemulonii or C. lusitaniae. Ideally, any strain of Candida that displays drug resistance should be sent for analysis to a reference laboratory," Colombo said.

Treatment options for a deadly liver cancer, fibrolamellar carcinoma, are severely lacking. Drugs that work on other liver cancers are not effective, and although progress has been made in identifying the specific genes involved in driving the growth of fibrolamellar tumors, these findings have yet to translate into any treatment. For now, surgery is the only option for those affected--mostly children and young adults with no prior liver conditions.

Sanford M. Simon and his group understood that patients dying of fibrolamellar could not afford to wait. "There are people who need therapy now," he says. So his group threw the kitchen sink at the problem and tested over 5,000 compounds, either already approved for other clinical uses or in clinical trials, to see whether any of the compounds could be repurposed to treat fibrolamellar. The team ultimately discovered a few classes of therapeutics that destroy fibrolamellar tumor cells growing in mice. Their findings are published in Cancer Discovery.

"We decided to be completely agnostic about what we thought would work--we tried everything," says Simon, head of the Laboratory of Cellular Biophysics. "To our surprise, we found a few compounds that work really well."

Faster drug discovery

In an ideal world, scientists perform extensive experiments to identify the perfect therapeutic target for a disease, then test a suite of drugs in model systems to pinpoint promising treatment options to hit the chosen target. The Simon lab is undergoing such experiments, but this process can take years, and the children and young adults who are sick now of fibrolamellar will likely never see the fruits of such labors.

So Simon took a parallel, expedited approach. After testing an extensive library of drugs on fibrolamellar tumor cells grown in mice over the course of several months, his team identified a few novel classes of therapeutics that appear to effectively kill fibrolamellar tumor cells, and further experiments provided some molecular explanations for why these drugs are so effective against a disease that has, until now, baffled physicians who treat liver cancer.

"Up to this point I've had to tell patients that we don't have any medicines that are proven to work," says Michael V. Ortiz, a pediatric oncologist at Memorial Sloan Kettering Cancer Center and a collaborator on the study. "It's really thrilling that we finally have some promising drugs to go after in clinical trials. And, since each individual responds differently, it's particularly exciting that we had multiple hits, which we can now test in combination with one another."

Treatment tailored for one

Building on these initial findings, Simon and his colleagues tested the compounds on human cells taken directly from patient tumors. They were able to test the cells against their lineup of drug candidates after growing them for only a few days, obtaining results similar to those observed in cells that took months to grow.

"Within three days, we can have therapeutically informative data, which is much faster than previous methods allowed," says Gadi Lalazar, an instructor in clinical investigation in the Simon laboratory and first author on the study. "Although there are some logistical hurdles and additional verification is needed, this could potentially be transformative for treating certain cancers."

The findings suggest that it may be unnecessary to screen new cancer drug candidates in cells grown in mice before testing them on human cells--an extra step that can cost cancer researchers many months. Given these results, physicians may soon be able to biopsy cells from a patient's tumor, subject those cells to a bevy of drug candidates until they find the most effective compound for that specific patient, and have a treatment plan ready in a matter of days--potentially transforming the landscape of precision medicine.

Advances in precision medicine

Simon's recent work was inspired by the 2015 precision medicine initiative begun in the Obama administration, which promised to change the face of medicine with a targeted approach, tailored to a patient's unique genetic composition, lifestyle, and environment.

"You don't want to give everyone with a limp the same treatment--you want it 'precisely targeted' based on whether they have twisted their ankle, broken a bone, or just have a splinter," says Simon.

Over the past six years, Simon has developed a series of model systems to help identify molecules known to drive cancers, known as oncogenes. But the key to applying precision medicine to cancer, Simon realized, is not blindly testing drugs against mutations or abnormally expressed genes--it's performing functional screenings that ask what drugs actually have an impact on the tumor in question.

The results of Simon's approach have now yielded the first therapeutics shown to eliminate fibrolamellar tumor cells, and new hope for people suffering from a deadly disease.

DALLAS - June 14, 2021 - Overweight cancer patients receiving immunotherapy treatments live more than twice as long as lighter patients, but only when dosing is weight-based, according to a study by cancer researchers at UT Southwestern Medical Center.

The findings, published in the Journal for ImmunoTherapy of Cancer, run counter to current practice trends, which favor fixed dosing, in which patients are given the same dose regardless of weight. The study included data on nearly 300 patients with melanoma, lung, kidney, and head and neck cancers over five years. Overweight patients were considered those with a body mass index, which accounts for height and weight, of 25 or more.

The researchers found that overweight patients did better with weight-based dosing, while lighter patients did better with fixed-dose immunotherapy. With weight-based dosing, overweight patients lived an average of more than 20 months compared with less than 10 months for lighter patients. With fixed dosing, both groups had similar outcomes, living an average of 16 months.

"Even when we accounted for differences in tumor and treatment types, overweight patients lived twice as long as smaller patients if they received weight-based dosing. However, there was no difference if they received fixed-dose immunotherapy," said senior author David Gerber, M.D., professor of internal medicine within the division of hematology and oncology at UT Southwestern, and associate director of clinical research in the Harold C. Simmons Comprehensive Cancer Center.

DARIEN, IL - According to a study of data from more than 163,000 Fitbit users, sleep duration increased slightly in 2020 during the COVID-19 pandemic compared with a similar timeframe in 2019.

Results show that mean sleep duration increased in nearly all groups by 5 to 11 minutes, compared with a mean decrease of 5 to 8 minutes seen over the same period in 2019. Sleep timing shifted later for nearly all groups. Sleep duration and bedtime variability decreased, largely due to fewer differences between weekday and weekend sleep.

"The most surprising thing we found was that, overall, sleep duration increased slightly, and sleep variability decreased slightly, during the most intense months of the pandemic," said lead author Michael Grandner, who has a doctorate in clinical psychology and is the director of the sleep and health research program at the University of Arizona College of Medicine. "It was also interesting to see that the degree of change in sleep was correlated with the degree of improvement in resting heart rate."

The researchers analyzed sleep variables extracted from data contributed by 163,524 deidentified, active Fitbit users from six major U.S. cities, representing areas particularly hard-hit by the pandemic: Chicago, Houston, Los Angeles, New York, San Francisco, and Miami. Deviation from similar timeframes in 2019 were examined.

"The results provide perhaps the largest study of objective sleep recordings from a geographically diverse general population sample during the height of the pandemic," said Grandner. "They are also important because they document important population trends, such as delayed bedtime and extended sleep, perhaps due to stay-at-home orders."