ReportWire

Tag: Clinical Trials

  • Ketamine shows efficacy for treatment-resistant depression

    Ketamine shows efficacy for treatment-resistant depression

    [ad_1]

    Newswise — A low-cost version of ketamine to treat severe depression has performed strongly in a double-blind trial that compared it with placebo.

    In research published today in the British Journal of Psychiatry, researchers led by UNSW Sydney and the affiliated Black Dog Institute found that more than one in five participants achieved total remission from their symptoms after a month of bi-weekly injections, while a third had their symptoms improve by at least 50 per cent. The study was a collaboration between six academic clinical mood disorder units in Australia and one in New Zealand and was funded by the Australian National Health and Medical Research Council (NHMRC).

    “For people with treatment-resistant depression – so those who have not benefitted from different modes of talk-therapy, commonly prescribed antidepressants, or electroconvulsive therapy – 20 per cent remission is actually quite good,” lead researcher Professor Colleen Loo says.

    “We found that in this trial, ketamine was clearly better than the placebo – with 20 per cent reporting they no longer had clinical depression compared with only 2 per cent in the placebo group. This is a huge and very obvious difference and brings definitive evidence to the field which only had past smaller trials that compared ketamine with placebo.”

    How the trial worked

    The researchers recruited 179 people with treatment-resistant depression. All were given an injection of either a generic form of ketamine that is already widely available in Australia as a drug for anaesthesia and sedation – or placebo. Participants received two injections a week in a clinic where they were monitored for around two hours while acute dissociative and sedative effects wore off – usually within the first hour. The treatment ran for a month and participants were asked to assess their mood at the end of the trial and one month later.

    As a double-blind trial, neither participants nor researchers administering the drug were aware which patients received generic ketamine or placebo, to ensure psychological biases were minimised. Importantly, a placebo was chosen that also causes sedation, to improve treatment masking. Midazolam is a sedative normally administered before a general anaesthetic, while in many previous studies the placebo was saline.

    “Because there are no subjective effects from the saline, in previous studies it became obvious which people were receiving the ketamine and which people received placebo,” Prof. Loo says.

    “In using midazolam – which is not a treatment for depression, but does make you feel a bit woozy and out of it – you have much less chance of knowing whether you have received ketamine, which has similar acute effects.”

    Other features of the recent trial that set it apart from past studies included accepting people into the trial who had previously received electroconvulsive therapy (ECT).

    “People are recommended ECT treatment for their depression when all other treatments have been ineffective,” Prof. Loo says.

    “Most studies exclude people who have had ECT because it is very hard for a new treatment to work where ECT has not.”

    Another difference about this trial was that the drug was delivered subcutaneously (injected into the skin) rather than by drip, thus greatly reducing time and medical complexity. The study is also the largest in the world to date that compares generic ketamine with placebo in treating severe depression.

    Much more affordable

    Apart from the positive results, one of the standout benefits of using generic ketamine for treatment-resistant depression is that it is much cheaper than the patented S-ketamine nasal spray currently in use in Australia. Where S-ketamine costs about $800 per dose, the generic ketamine is a mere fraction of that, costing as little as $5, depending on the supplier and whether the hospital buys it wholesale. On top of the cost for the drug, patients need to pay for the medical care they receive to ensure their experience is safe – which at Black Dog Institute clinics, comes to $350 per session.

    “With the S-ketamine nasal spray, you are out of pocket by about $1200 for every treatment by the time you pay for the drug and the procedure, whereas for generic ketamine, you’re paying around $300-350 for the treatment including the drug cost,” Prof. Loo says.

    She adds that for both S-ketamine and generic ketamine treatments, the positive effects often wear off after a few days to weeks, so ongoing treatment may be required, depending on someone’s clinical situation. But the prohibitive costs of the drug and procedure make this an unsustainable proposition for most Australians.

    “This is why we’re applying for a Medicare item number to fund this treatment now, because it’s such a powerful treatment.

    “And if you consider that many of these people might spend many months in hospital, or be unable to work and are often quite suicidal, it’s quite cost effective when you see how incredibly quickly and powerfully it works. We’ve seen people go back to work, or study, or leave hospital because of this treatment in a matter of weeks.”

    The researchers will next be looking at larger trials of generic ketamine over longer periods, and refining the safety monitoring of treatment.

    ENDS

    Participating trial sites

    • UNSW / Black Dog Institute
    • Royal Prince Alfred Hospital / University of Sydney
    • NeuroCentrix Research Institute
    • Royal Adelaide Hospital / University of Adelaide
    • Monash Alfred Psychiatry Research Centre / Monash University
    • University of Otago
    • Gold Coast University Hospital

     

    Institutions of non-site collaborators

    • Deakin University
    • University of Newcastle
    • The George Institute for Global Health
    • University of Western Australia

    [ad_2]

    University of New South Wales

    Source link

  • A Gaping Hole in Cancer-Therapy Trials

    A Gaping Hole in Cancer-Therapy Trials

    [ad_1]

    This article was originally published by Undark Magazine.

    In October 2021, 84-year-old Jim Yeldell was diagnosed with Stage 3 lung cancer. The first drug he tried disrupted his balance and coordination, so his doctor halved the dose to minimize these side effects, Yeldell recalls. In addition, his physician recommended a course of treatment that included chemotherapy, radiation, and a drug targeting a specific genetic mutation. This combination can be extremely effective—at least in younger people—but it can also be “incredibly toxic” in older, frail people, says Elizabeth Kvale, a palliative-care specialist at Baylor College of Medicine, and also Yeldell’s daughter-in-law.

    Older patients are often underrepresented in clinical trials of new cancer treatments, including the one offered to Yeldell. As a result, he only learned of the potential for toxicity because his daughter-in-law had witnessed the treatment’s severe side effects in the older adults at her clinic.

    This dearth of age-specific data has profound implications for clinical care, because older adults are more likely than younger people to be diagnosed with cancer. In the U.S., approximately 42 percent of people with cancer are over the age of 70—a number that could grow in the years to come—yet they comprise less than a quarter of the people in clinical trials to test new cancer treatments. Many of those who do participate are the healthiest of the aged, who may not have common age-related conditions like diabetes or poor kidney or heart function, says Mina Sedrak, a medical oncologist and the deputy director of the Center for Cancer and Aging at City of Hope National Medical Center.

    For decades, clinical trials have tended to exclude older participants for reasons that include concerns about preexisting conditions and other medications and participants’ ability to travel to trial locations. As a result, clinicians cannot be as certain that approved cancer drugs will work as predicted in clinical trials for the people most likely to have cancer. This dearth of data means that older cancer patients must decide if they want to pursue a treatment that might yield fewer benefits—and cause more side effects—than it did for younger people in the clinical trial.

    This evidence gap extends across the spectrum of cancer treatments—from chemotherapy and radiation to immune-checkpoint inhibitors—with sometimes-dire results. Many forms of chemotherapy, for example, have proved to be more toxic in older adults, a discovery that came only after the drugs were approved for use in this population. “This is a huge problem,” Sedrak says. In an effort to minimize side effects, doctors will often tweak the dose or duration of medications that are given to older adults, but these physicians are doing this without any real guidance.

    Despite recommendations from funders and regulators, as well as extensive media coverage, not much has changed in the past three decades. “We’re in this space where everyone agrees this is a problem, but there’s very little guidance on how to do better for older adults,” Kvale says. “The consequences in the real world are stark.”

    Post-approval studies of cancer drugs have helped shed light on the disconnect between how these drugs are used in clinical trials and how they are used in clinics around the country.

    Read: America’s most popular drug has a puzzling side effect. We finally know why.

    For example, when Cary Gross, a physician and cancer researcher at Yale, set out to study the use of a new kind of cancer drug known as an immune-checkpoint inhibitor, he knew that most clinicians were well aware that clinical trials overlooked older patients. Gross’s research team suspected that some doctors might be wary of offering older adults the treatments, which work by preventing immune cells from switching off, thus allowing them to kill cancer cells. “Maybe they’re going to be more careful,” he says, and offer the intervention to younger patients first.

    But in a 2018 analysis of more than 3,000 patients, Gross and his colleagues found that within four months of approval by the FDA, most patients eligible to receive a class of immune-checkpoint inhibitors were being prescribed the drugs. And the patients receiving this treatment in clinics were significantly older than those in the clinical trials. “Oncologists were very ready to give these drugs to the older patients, even though they’re not as well represented,” Gross says.

    In another analysis, published this year, Gross and his colleagues examined how these drugs helped people diagnosed with certain types of lung cancer. The team found that the drugs extended the life of patients under the age of 55 by a median of four and a half months, but only by a month in those over the age of 75.

    The evidence doesn’t suggest that checkpoint inhibitors aren’t helpful for many patients, Gross says. But it’s important to identify which particular populations are helped the most by these drugs. “I thought that we would see a greater survival benefit than we did,” he says. “It really calls into question how we’re doing research, and we really have to double down on doing more research that includes older patients.”

    People over the age of 65 don’t fare well with other types of cancer treatments either. About half of older patients with advanced cancer experience severe and even potentially life-threatening side effects with chemotherapy, which can lead oncologists to lower medication doses, as in Yeldell’s case.

    There’s a strong connection between the lack of evidence from clinical trials and worse outcomes in the clinic, according to Kvale. “There’s a lot of enthusiasm for these medicines that don’t seem so toxic up front,” she says, “but understanding where they do or don’t work well is key—not just because of the efficacy, but because those drugs are almost toxically expensive sometimes.”

    Since the earliest reports of this data gap, regulators and researchers have tried to fix the problem. Changes to clinical trials have, in principle, made it easier for older adults to sign up. For instance, fewer and fewer studies have an upper age limit for participants. Last year, the FDA issued guidance to industry-funded trials recommending the inclusion of older adults and relaxing other criteria, to allow for participants with natural age-related declines. Still, the problem persists.

    When Sedrak and his colleagues set out to understand why the needle had moved so little over the past few decades, their analysis found a number of explanations, beginning with eligibility criteria that may inadvertently disqualify older adults. Physicians may also be concerned about their older patients’ ability to tolerate unknown side effects of new drugs. Patients and caregivers share these concerns. The logistics of participation can also prove problematic.

    “But of all these, the main driving force, the upstream force, is that trials are not designed with older adults in mind,” Sedrak says. Clinical trials tend to focus on survival, and although older adults do care about this, many of them have other motivations—and concerns—when considering treatment.

    Clinical trials are generally geared toward measuring improvements in health: They may track the size of tumors or months of life gained. These issues aren’t always top of mind for older adults, according to Sedrak. He says he’s more likely to hear questions about how side effects may influence the patient’s cognitive function, ability to live independently, and more. “We don’t design trials that capture the end points that older adults want to know,” he says.

    Read: Hiccups have a curious connection to cancer

    As a group, older adults do experience more side effects, sometimes so severe that the cure rivals the disease. In the absence of evidence from clinical trials, clinicians and patients have tried to find other ways to predict how a patient’s age might influence their response to treatment. In Yeldell’s case, discussions with Kvale and his care team led him to choose a less intensive course of treatment that has kept his cancer stable since October 2022. He continues to live in his own home and exercises with a trainer three times a week.

    For others trying to weigh their choices, researchers are developing tools that can create a more complete picture by accounting for a person’s physiological age. In a 2021 clinical trial, Supriya Mohile, a geriatric oncologist at the University of Rochester, and her colleagues tested the use of one such tool, known as a geriatric assessment, on the side effects and toxicity of cancer treatments. The tool assesses a person’s biological age based on various physiological tests.

    The team recruited more than 700 people with an average age of 77 who were about to embark on a new cancer-treatment regimen with a high risk of toxicity. Roughly half of the participants received guided treatment-management recommendations based on a geriatric assessment, which their oncologists factored into their treatment decisions. Only half of this group of patients experienced serious side effects from chemotherapy, compared with 71 percent of those who didn’t receive specialized treatment recommendations.

    This type of assessment can help avoid both undertreatment of people who might benefit from chemotherapy and overtreatment of those at risk of serious side effects, Mohile says. It doesn’t compensate for the lack of data on older adults. But in the absence of that evidence, tools such as geriatric assessment can help clinicians, patients, and families make better-informed choices. “We’re kind of going backwards around the problem,” Mohile says. Although geriatric oncologists recognize the need for better ways to make decisions, she says, “I think the geriatric assessment needs to be implemented until we have better clinical-trial data.”

    Since 2018, the American Society of Clinical Oncology has recommended the use of geriatric assessment to guide cancer care for older patients. But clinicians have been slow to follow through in their practice, in part because the assessment doesn’t necessarily show any cancer-specific benefits, such as tumors shrinking and people living longer. Instead, the tool’s main purpose is to improve quality of life. “We need more prospective therapeutic trials in older adults, but we also need all of these other mechanisms to be funded,” Mohile says, “So we actually know what to do for older adults who are in the real world.”

    [ad_2]

    Jyoti Madhusoodanan

    Source link

  • Australia is the first country to let patients with depression or PTSD be prescribed psychedelics

    Australia is the first country to let patients with depression or PTSD be prescribed psychedelics

    [ad_1]

    SYDNEY — Australia is now the first country to allow psychiatrists to prescribe certain psychedelic substances to patients with depression or post-traumatic stress disorder.

    Beginning Saturday, Australian physicians can prescribe doses of MDMA, also known as ecstasy, for PTSD. Psilocybin, the psychoactive ingredient in psychedelic mushrooms, can be given to people who have hard-to-treat depression. The country put the two drugs on the list of approved medicines by the Therapeutic Goods Administration.

    Scientists in Australia were surprised by the move, which was announced in February but took effect July 1. One scientist said it puts Australia “at the forefront of research in this field.”

    Chris Langmead, deputy director of the Neuromedicines Discovery Centre at the Monash Institute of Pharmaceutical Sciences, said there have been very few advancements on treatment of persistent mental health issues in the last 50 years.

    The growing cultural acceptance has led two U.S. states to approve measures for their use: Oregon was the first to legalize the adult use of psilocybin, and Colorado’s voters decriminalized psilocybin in 2022. Days ago, President Joe Biden’s youngest brother said in a radio interview that the president has been “very open-minded” in conversations the two have had about the benefits of psychedelics as a form of medical treatment.

    The U.S. Food and Drug Administration designated psilocybin as a “breakthrough therapy” in 2018, a label that’s designed to speed the development and review of drugs to treat a serious condition. Psychedelics researchers have benefited from federal grants, including Johns Hopkins, and the FDA released draft guidance late last month for researchers designing clinical trials testing psychedelic drugs as potential treatments for a variety of medical conditions.

    Still, the American Psychiatric Association has not endorsed the use of psychedelics in treatment, noting the FDA has yet to offer a final determination.

    And medical experts in the U.S. and elsewhere, Australia included, have cautioned that more research is needed on the drugs’ efficacy and the extent of the risks of psychedelics, which can cause hallucinations.

    “There are concerns that evidence remains inadequate and moving to clinical service is premature; that incompetent or poorly equipped clinicians could flood the space; that treatment will be unaffordable for most; that formal oversight of training, treatment, and patient outcomes will be minimal or ill-informed,” said Dr. Paul Liknaitzky, head of Monash University’s Clinical Psychedelic Lab.

    Plus, the drugs will be expensive in Australia — about $10,000 (roughly $6,600 U.S. dollars) per patient for treatment.

    Litnaitzky said the opportunity for Australians to access the drugs for specific conditions is unique.

    “There’s excitement about drug policy progress,” he said, “… about the prospect of being able to offer patients more suitable and tailored treatment without the constraints imposed by clinical trials and rigid protocols.”

    [ad_2]

    Source link

  • New Preliminary Findings on Potential Response Indicator of Rakuten Medical’s Alluminox Treatment from Phase 2 Window of Opportunity Study at SNMMI 2023

    New Preliminary Findings on Potential Response Indicator of Rakuten Medical’s Alluminox Treatment from Phase 2 Window of Opportunity Study at SNMMI 2023

    [ad_1]

    – 18F-FDG PET/CT imaging 1 day after Alluminox treatment with ASP-1929 may serve as a potential indicator of treatment response

    – The oral presentation was given by Dr. Lindenberg of NCI, NIH, which is collaborating with Rakuten Medical to conduct ASP-1929-103, the Company’s very first study for operable cancer

     

    Newswise — SAN DIEGO, June 30, 2023 /PRNewswire/ — Rakuten Medical, Inc., a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, today announced that new interim evaluation data from the ASP-1929-103 study has been presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2023 Annual Meeting held from June 24 to 27.  ASP-1929-103 is a Phase 2, open-label, single-arm, window of opportunity study* of Alluminox treatment (photoimmunotherapy: PIT) using an antibody-dye conjugate ASP-1929 with fluorescence imaging (ClinicalTrials.gov Identifier: NCT05182866) in patients with operable primary or recurrent head and neck squamous cell carcinoma (HNSCC) or cutaneous squamous cell carcinoma (cuSCC).  

    The oral presentation was given by Liza Lindenberg, M.D., of the National Cancer Institute (NCI), which has a Cooperative Research and Development Agreement to conduct ASP-1929-103 study. ASP-1929-103 is the very first clinical trial of Alluminox treatment in operable cancer. As part of this trial, early time point (1 day) 18F-FDG PET/CT imaging was investigated as a potential response indicator of Alluminox treatment.

    The preliminary, descriptive imaging analysis based on interim evaluation of 6 patients in ASP-1929-103 study presented during the meeting showed that 18F-FDG PET/CT imaging demonstrates a therapeutic response 1 day after Alluminox treatment using ASP-1929.  PET/CT is an imaging modality for combined acquisition of positron emission tomography (PET) and computed tomography (CT) pictures. 18F-fluorodeoxyglucose (18F-FDG) is the radiotracer used for this PET study.  Like glucose (sugar), 18F-FDG  is taken up by cells, particularly rapidly dividing cells such as cancer cells. Following uptake, 18F-FDG accumulates in the cytoplasm rather than undergoing further metabolism which results in signal amplification from labeled cells.

    Key findings presented at SNMMI 2023
    “Early 18F-FDG Response after Near-Infrared Photoimmunotherapy for Head and Neck and Cutaneous Squamous Cell Carcinoma” (Abstract: P50) presented by Liza Lindenberg, M.D., Molecular Imaging Branch, NCI, NIH

    –  18F FDG PET/CT demonstrates a therapeutic response 1 day after a single ASP-1929 PIT treatment
    –  Delayed 18F-FDG PET/CT imaging may decrease confounding inflammatory uptake on scans
    –  Pathologic tumor response may add complementary information to 18F-FDG PET/CT in PIT

    Disclaimer: These early findings may change upon trial completion and final data analysis.

    ASP-1929-103 study overview
    ASP-1929-103 is a Phase 2, open-label, single-arm, window of opportunity study* of Alluminox treatment (PIT) using an anti-EGFR antibody-dye conjugate, ASP-1929 with fluorescence imaging in patients with operable primary or recurrent HNSCC or cuSCC. The study, sponsored by Rakuten Medical in collaboration with NCI and Shimadzu Corporation (Shimadzu), will enroll 22 patients in the US to evaluate the efficacy and safety of a single Alluminox treatment using ASP-1929 administered prior to standard of care surgical tumor resection.  The feasibility of the Shimadzu fluorescence imaging system for real-time monitoring and recording of the fluorescence of the IRDye® 700DX portion of ASP-1929 will also be assessed.

    *  Window of opportunity study takes place in the period between a cancer diagnosis and the subsequent initiation of standard treatment, during which, the patient receives a non-standard drug or treatment of interest over a short period of time 1.2.
    1.  Aroldi F, Lord SR. Window of opportunity clinical trial designs to study cancer metabolism. Br J Cancer. 2020;122(1):45-51. doi:10.1038/s41416-019-0621-4.
    2.  Schmitz S, Duhoux F, Machiels JP. Window of opportunity studies: Do they fulfil our expectations? Cancer Treat Rev. 2016 Feb;43:50-7. doi: 10.1016/j.ctrv.2015.12.005. Epub 2015 Dec 31. PMID: 26827692.

    About Rakuten Medical, Inc.
    Rakuten Medical, Inc. is a global biotechnology company developing and commercializing precision, cell targeting therapies based on its proprietary Alluminox™ platform, which, in pre-clinical studies, has been shown to induce rapid and selective cell killing and tumor necrosis. Alluminox therapies have not yet been approved outside of Japan. Rakuten Medical is committed to its mission to conquer cancer by delivering our innovative treatments as quickly as possible to as many patients as possible all over the world. The company has offices in 6 countries, including the United States, where it is headquartered, Japan, the Netherlands, Taiwan, Switzerland and India. For more information, visit www.rakuten-med.com.

    About Alluminox™ platform 
    The Alluminox™ platform is an investigational technology platform based on a cancer therapy called photoimmunotherapy, which was developed by Dr. Hisataka Kobayashi and team from the National Cancer Institute in the United States. Rakuten Medical is developing the Alluminox platform as a technology consisting of a drug, device, and other related components. The drug component of the platform consists of a targeting moiety conjugated with one or more dyes leading to selective cell surface binding. The device component consists of a light source that locally illuminates the targeted cells with light to transiently activate the drug. Pre-clinical data have shown that this activation elicits rapid and selective necrosis of targeted cells through a biophysical process that compromises the membrane integrity of the targeted cells. Therapies developed on the Alluminox platform may also result in local and systemic innate and adaptive immune activation due to immunogenic cell death of the targeted cancer cells and/or the removal of targeted immunosuppressive cells within the tumor microenvironment. Outside of Japan, Alluminox therapies have not yet been approved by any regulatory authority.

    About ASP-1929
    Rakuten Medical’s first pipeline drug developed on its Alluminox™ platform is ASP-1929, an antibody-dye conjugate comprised of the antibody cetuximab and IRDye® 700DX, a light activatable dye. ASP-1929 binds to epidermal growth factor receptor (EGFR), a cancer antigen expressed in multiple types of solid tumors, including head and neck, breast, lung, colorectal, prostate and pancreatic cancers. After binding to cancer cells, ASP-1929 is locally activated by   illumination with red light (690 nm), emitted by a laser device system to produce a photochemical reaction. This reaction is believed to cause damage to the membrane of cancer cells, leading to selective necrosis of cancer cells. ASP-1929 received Fast Track designation from the U.S. Food and Drug Administration (FDA) in January 2018, and is currently under investigation in a global Phase 3 clinical trial for recurrent head and neck cancer. In Japan, ASP-1929 received marketing approval from the Japanese Ministry of Health, Labor, and Welfare for unresectable locally advanced or recurrent head and neck cancer in September 2020, under the Sakigake Designation System and the Conditional Early Approval System. Outside of Japan, ASP-1929 has not yet been approved by any regulatory authority.

    Forward Looking Statements 
    This press release contains forward looking statements that correspond to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements include various risks, uncertainties, and assumptions that may cause Rakuten Medical’s business plans and results to differ from the anticipated results and expectations expressed in these statements. These “forward looking statements” contain information about the status and development of our products, including the Alluminox™ platform, as well as other regulatory and marketing authorization efforts, the potential benefits, efficacy, and safety of therapies created using the Alluminox platform, and the status of regulatory filings. The approval and commercial success of the product may not be achieved. Forward looking statements relate to the potential benefits, efficacy, and safety of our therapies, and the status of regulatory filings. Such statements may include words such as “expect,” “believe,” “hope,” “estimate,” “looks as though,” “anticipate,” “intend,” “may,” “suggest,” “plan,” “strategy,” “will,” and “do”, and are based on our current beliefs. In addition, this press release uses terms such as “important,” “notable,” and “abnormal” to express opinions about clinical trial data. Ongoing clinical trial studies include various risks and uncertainties, in particular, problems that arise during the manufacturing stage of our therapies, the occurrence of adverse safety events, situations in failure to demonstrate therapeutic benefits, and other various risks and uncertainties, both reasonable and unreasonable. For this reason, actual results, including regulatory approvals and uncertainties in the commercialization process of our therapies, may differ from published information. Except to the extent required by applicable law, we undertake no obligation to publicly update this or any other forward-looking statement, whether because of new information, future developments or events, changes in assumptions, changes in the factors affecting forward-looking statements. If one or more forward-looking statement(s) is updated, no inference should be drawn that additional updates will be made to those or other forward-looking statements.

     

    Contact Us

    [ad_2]

    Rakuten Medical, Inc.

    Source link

  • Atlantic Health System Cancer Care enrolls first patient in eastern US in groundbreaking non-Hodgkin lymphoma drug trial

    Atlantic Health System Cancer Care enrolls first patient in eastern US in groundbreaking non-Hodgkin lymphoma drug trial

    [ad_1]

    Newswise — MORRISTOWN, N.J. – JUNE 29, 2023 – Atlantic Health System Cancer Care is the only site on the east coast of the United States to enroll a patient in a new trial designed to test a groundbreaking approach to treating non-Hodgkin lymphoma. The patient enrolled received their first dose of the medication last week and is only the 20th patient in the country to receive this novel treatment.

    Developed by Caribou Biosciences, Inc., the medicine leverages chimeric antigen receptor (CAR) T-cell therapy, the practice of using modified versions of the body’s own T-lymphocyte immune cells to find, target and destroy cancer cells. However, unlike in traditional CAR T-cell therapies, where blood from the patient is withdrawn, then modified in a lab, and then infused back into the body, this medication is created using already donated blood, modified to match the patient, thus cutting down on the amount of time needed to prepare treatment and potentially resulting in a better match for the patient. The T-cells are modified using CRISPR genetic material editing technology.

    The treatment is provided at Atlantic Health System’s Morristown Medical Center in the Carol G. Simon Cancer Center by Mohamad Cherry, MD, Medical Director, Hematology/Oncology and Medical Director, Atlantic Cellular Therapy Program, and in partnership with the Translational Genomics Research Institute (TGen) of Phoenix, Arizona via the Breakthrough Oncology Accelerator, a pioneering research and clinical collaboration designed to improve patient access to the most innovative and sophisticated therapies for cancer.

    “Recent years have seen remarkable advancements in the ability to treat cancers of all types, but the next step in the treatment of blood cancers such as non-Hodgkin lymphoma may well be the groundbreaking, customized care we are researching as part of this trial,” said Dr. Cherry. “The ability to enter patients into treatment faster and with greater efficacy would be a tremendous win for patients and the physicians committed to helping them on their healing journey.”

    Atlantic Health System is already involved in a number of studies examining the amazing potential of CAR T-cell therapies treating leukemia and lymphoma.

    “The Atlantic Health System Cancer Care team is committed to providing extraordinary care to every patient in a way that is specific to that particular patient,” said Eric D. Whitman, MD, Medical Director, Atlantic Health System Cancer Care and Director, Atlantic Melanoma Center. “This exciting study holds the potential to craft even more tailored and specific medications and we are proud to be part of it.”

    This first-in-human trial involves non-Hodgkin lymphoma patients for whom initial treatment was unsuccessful or are experiencing a return of the disease. You can learn more about the study at the National Institutes of Health website for clinical trials.

    Visit the Atlantic Health System website to learn more about the exciting research underway in cancer care and other specialties.

    About Atlantic Health System Cancer Care

    Atlantic Health System Cancer Care offers an unparalleled network of cancer specialists and resources for more than 70,500 patients annually through its flagship Carol G. Simon Cancer Center at Morristown and Overlook medical centers, as well as its comprehensive oncology programs at Chilton, Hackettstown and Newton medical centers. With more than 250 cancer specialists and medical professionals, all five hospitals and Atlantic Medical Group have been recognized nationally for their role in advancing the fight against cancer.

    Atlantic Health System Cancer Care is the lead affiliate of Atlantic Health Cancer Consortium (AHCC) – the only New Jersey-based National Cancer Institute (NCI) Community Oncology Research Program (NCORP).  Atlantic Health System is affiliated with the Translational Genomics Research Institute (TGen) of Phoenix, Arizona, and together they have created the Breakthrough Oncology Accelerator, a pioneering research and clinical collaboration designed to improve patient access to the most innovative and sophisticated therapies for cancer.

    About Atlantic Health System

    Atlantic Health System is at the forefront of medicine, setting standards for quality health care in New Jersey, Pennsylvania and the New York metropolitan area. Powered by a workforce of 19,000 team members and 5,440 affiliated physicians dedicated to building healthier communities, Atlantic Health System serves more than half of the state of New Jersey including 12 counties and 6.2 million people. The not-for-profit system offers more than 400 sites of care, including its seven hospitals: Morristown Medical Center in Morristown, NJ, Overlook Medical Center in Summit, NJ, Newton Medical Center in Newton, NJ, Chilton Medical Center in Pompton Plains, NJ, Hackettstown Medical Center in Hackettstown, NJ, Goryeb Children’s Hospital in Morristown, NJ, Atlantic Rehabilitation Institute in Madison, NJ and through its partnership with CentraState Healthcare System in Freehold, NJ.

    The system includes Atlantic Medical Group, part of a physician enterprise that makes up one of the largest multispecialty practices in New Jersey with more than 1,600 physicians and advance practice providers. Joined with Atlantic Accountable Care Organization and Optimus Healthcare Partners they form part of Atlantic Alliance, a Clinically Integrated Network of more than 2,500 health care providers throughout northern and central NJ.

    Atlantic Health System provides care for the full continuum of health care needs through 24 urgent care centers, Atlantic Visiting Nurse and Atlantic Anywhere Virtual Visits. Facilitating the connection between these services on both land and air is the transportation fleet of Atlantic Mobile Health.

    Atlantic Health System leads the Healthcare Transformation Consortium, a partnership of six regional hospitals and health systems dedicated to improving access and affordability and is a founding member of the PIER Consortium – Partners in Innovation, Education, and Research – a streamlined clinical trial system that will expand access to groundbreaking research across five health systems in the region.

    Atlantic Health System has a medical school affiliation with Thomas Jefferson University and is home to the regional campus of the Sidney Kimmel Medical College at Morristown and Overlook Medical Centers and is the official health care partner of the New York Jets.

     ###

    [ad_2]

    Atlantic Health System

    Source link

  • America’s Most Popular Drug Has a Puzzling Side Effect. We Finally Know Why.

    America’s Most Popular Drug Has a Puzzling Side Effect. We Finally Know Why.

    [ad_1]

    Statins, one of the most extensively studied drugs on the planet, taken by tens of millions of Americans alone, have long had a perplexing side effect. Many patients—some 5 percent in clinical trials, and up to 30 percent in observational studies—experience sore and achy muscles, especially in the upper arms and legs. A much smaller proportion, less than 1 percent, develop muscle weakness or myopathy severe enough that they find it hard to “climb stairs, get up from a sofa, get up from the toilet,” says Robert Rosenson, a cardiologist at Mount Sinai. He’s had patients fall on the street because they couldn’t lift their leg over a curb.

    But why should an anticholesterol drug weaken muscles in the arms and legs? Recently, two groups of scientists stumbled upon an answer. They didn’t set out to study statins. They weren’t studying cholesterol at all. They were hunting for genes behind a rare disease called limb girdle muscle dystrophy, in which muscles of the upper arms and legs—sound familiar?—become weak and waste away. After both teams tracked the disease through a handful of families in the U.S. and a Bedouin family in Israel, their suspicions separately landed on mutations in a gene encoding a particularly intriguing enzyme.

    The enzyme is known as HMG-CoA reductase, and to doctors, it is not obscure. It is, in fact, the very enzyme that statins block in the process of halting cholesterol production. And so, the answers to two mysteries suddenly became clear at once: Dysfunction in this enzyme causes muscle weakness from both limb girdle muscular dystrophy and statins.

    This connection between a rare disease and a common drug stunned the researchers. “It seemed too good to be true,” says Joel Morales-Rosado, a pathologist who worked on one of the studies as a postdoctoral researcher at the Mayo Clinic. “One of the first things you learn in medical school is association between statins and myopathy.” Now the answer as to why— along with a potential treatment for it—has emerged from the DNA of just a few patients living with a seemingly unrelated genetic disease.

    The first patient the Mayo team studied had been showing signs of limb girdle muscular dystrophy since he was a child, and his symptoms worsened over time until he lost the ability to walk or breathe with ease. (The disease can also affect large muscles in the torso.) Now in his 30s, he wanted to know the genetic cause of his disease before having children and potentially passing it on to them. His two brothers had the disease as well. So the team looked for genes in which all three brothers had mutations in both copies, which is how they zeroed in on the gene for HMG-CoA reductase.

    Six more patients from four other families confirmed the link. They too all had mutations in the same gene, and they too were all diagnosed with some degree of limb girdle muscular dystrophy. (Interestingly, for reasons we don’t entirely understand, they all have normal or low cholesterol.)

    Unbeknownst to the Mayo team, a group of researchers halfway around the world was already studying a large Bedouin family with a history of limb girdle muscular dystrophy. This family also carried mutations in the gene encoding HMG-CoA reductase. Those afflicted began experiencing minor symptoms in their 30s, such as muscle cramps, that worsened over time. The oldest family members, in their late 40s or 50s, had lost all movement in their arms and legs. One bedridden woman had to be ventilated full-time through a hole in her windpipe. Another had died in their mid-50s, Ohad Birk, a geneticist and doctor at Ben-Gurion University of the Negev, in Israel, told me. When his team saw that this family had the mutations in HMG-CoA reductase, they too immediately recognized the potential link to statins.

    This pair of studies in the U.S. and Israel “really strongly suggests” that statins cause muscle damage via the same HMG-CoA reductase pathway, says Andrew Mammen, a neurologist at the National Institutes of Health who was not involved in either study. The enzyme’s role had been suspected, he told me, but “it had never been proven, especially in humans.” (Questions still remain, however. The enzyme, for example, is found in tissues throughout the body, so why do these common side effects show up in muscles specifically?) Rosenson, at Mount Sinai, wondered if variations in this gene could explain why statins don’t affect everyone the same. Perhaps patients who suffer particularly severe muscle side effects already have less functional versions of the enzyme, which becomes problematic only when they start taking statins, which reduce its function even further. This research might end up concretely improving the life of at least some of the patients most severely affected by statins.

    That’s because Birk’s team in Israel did not stop at simply identifying the mutation. For two decades, he and his colleagues have been studying genetic disorders in this Bedouin community in the Negev and developing genetic tests so parents can avoid passing them on to their children. (Cousin marriages are traditional there, and when two parents are related, they are more likely to carry and pass on the same mutation to a child.) With limb girdle muscular dystrophy, his team went one step further than usual: They found a drug to treat it.

    This drug, called mevalonolactone, allows muscle cells to function more normally even without the HMG-CoA reductase enzyme. Birk’s team first tested it in mice given doses of statins high enough to weaken their limbs; those also given mevalonolactone continued to crawl and even hang upside down on a wire just fine. They seemed to suffer no ill effects. When that experimental drug was given to the Bedouin woman bedridden with limb girdle muscular dystrophy, she also started regaining control of her arms and legs. She could eventually lift her arm, sit up by herself, raise her knees, and even feed her grandchild on her own. It was a dramatic improvement. Birk told me he has since heard about dozens of patients with limb girdle muscular dystrophy around the world who may benefit from this experimental drug.

    Mammen and others think the drug could help a small subset of patients who take statins as well. However, the majority of patients—those with relatively minor pains or weaknesses that go away after they switch statins or have their dosage reduced—probably don’t need this new treatment. It probably even undermines the whole point of taking statins: Mevalonolactone eventually gets turned into cholesterol in the body, so “you’re basically supplying the building blocks for making more cholesterol,” Mammen said. But for some people, numbering in the thousands, severe muscle weakness does not go away even after they stop taking statins. These patients have developed antibodies to HMG-CoA reductase, which Mammen suspects continue to bind and disable the enzyme.

    Mammen is eager for these patients to try mevalonolactone, and he’s been in touch with Birk, who unfortunately doesn’t have enough of the drug to share. In fact, he doesn’t even have enough to treat all of the other family members in Israel who are clamoring for it. “We’re not a factory. We’re a research lab,” Birk told me. Mevalonolactone is available as a research chemical, but that’s not pure and safe enough for human consumption. Birk’s graduate student Yuval Yogev had to manufacture the drug himself by genetically engineering bacteria to make mevalonolactone, which he then painstakingly purified. Making a drug to this standard is a huge amount of work, even for commercial labs. Birk is looking for a pharmaceutical company that could manufacture the drug at scale—for both patients with limb girdle muscular dystrophy and those with the most severe forms of statin-associated muscle damage.

    Back in 1980, the very first person to receive an experimental dose of statins suffered muscle weakness so severe, she could not walk. (She had been given an extremely high dose.) Forty years later, muscle pain and weakness are still common reasons patients quit these very effective drugs. This recent breakthrough is finally pointing researchers toward a better understanding of statins’ toll on muscles, even if they still can’t fix it for everyone.

    [ad_2]

    Sarah Zhang

    Source link

  • Prompt testosterone treatment improves mental health of transgender, gender-diverse people

    Prompt testosterone treatment improves mental health of transgender, gender-diverse people

    [ad_1]

    Newswise — Receiving rapid access to testosterone therapy reduced feelings of gender dysphoria and led to a clinically significant reduction in depression as well as a 50% reduction in suicidality among transgender and gender diverse adults, according to research being presented Sunday at ENDO 2023, the Endocrine Society’s annual meeting in Chicago.

    “This is the world-first randomized clinical trial supporting the significant benefits of testosterone in reducing gender dysphoria, depression and suicidality in trans individuals desiring commencement of testosterone,” said Brendan Nolan, M.B.B.S., F.R.A.C.P., a Ph.D. candidate at the University of Melbourne (Austin Health) in Melbourne, Australia. 

    Gender dysphoria occurs when a person feels distressed that their gender identity does not align with the sex assigned at birth. When an individual’s gender identity is not respected and the individual cannot access medical care, it can result in higher psychological problem scores and can raise the person’s risk of committing suicide or other acts of self-harm.

    Nolan and colleagues sought to understand the impact of testosterone therapy compared with no treatment on gender dysphoria, depression, and suicidality in trans adults seeking masculinization.

    The three-month open-label randomized controlled trial included 64 transgender adults who were able to start testosterone therapy immediately (intervention group) compared with those who were on a standard waiting list of three months prior to beginning testosterone. The purpose of this segmentation was to ensure no person would have to prolong waiting to begin treatment beyond standard care practices.

    People who were able to begin treatment immediately showed decreased gender dysphoria and a clinically significant decrease in depression and suicidal ideation compared with study participants on the wait list.

    Suicidal ideation resolved in 11 (52%) people with immediate testosterone therapy, compared with 1 (5%) given standard care, according to results from the Patient Health Questionnaire-9.

    “Our findings illustrate the significant mental health benefits of early access to testosterone treatment and should provide an impetus for clinicians to ensure timely access to gender-affirming hormone therapy,” Nolan said. 

    # # #

    Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

    The Society has more than 18,000 members, including scientists, physicians, educators, nurses and students in 122 countries. To learn more about the Society and the field of endocrinology, visit our site at www.endocrine.org. Follow us on Twitter at @TheEndoSociety and @EndoMedia.

    [ad_2]

    Endocrine Society

    Source link

  • Major step forward reduces mortality in kidney failure patients

    Major step forward reduces mortality in kidney failure patients

    [ad_1]

    Newswise — Mortality in patients with kidney failure has been found to be 23% lower among those treated with high dose haemodiafiltration compared to those treated with high flux haemodialysis, according to new research from the CONVINCE consortium led by University Medical Center Utrecht.

    The study, published today in the New England Journal of Medicine, is the first international, randomised trial to compare the two treatments. The findings indicate that wider use of high dose haemodiafiltration would have clear benefits for patients.

    Chronic kidney disease is a leading global health problem that affects an estimated 830 million people globally. When the kidneys can no longer do their job, dialysis is used to clean the blood by removing waste products, a function normally performed by the kidneys themselves. Around four million people are on dialysis worldwide.

    Haemodialysis is the most common form of dialysis used in the treatment for kidney failure1. Though it has improved over the years, it is not good at removing larger molecules from the blood. Haemodiafiltration is a newer technology that can remove larger molecules, but it is not suitable for all patients due to the fact that it requires a higher blood flow rate to be effective. Previous studies have failed to conclusively prove that one method is more effective than the other.

    The CONVINCE trial has been led by researchers at UMC Utrecht together with collaborators at University College London (UCL), Charité Universitätsmedizin Berlin, University of Bari, The George Institute for Global Health and Imperial College London, along with dialysis providers Fresenius Medical Care, Diaverum and B. Braun Avitum. It is the first multinational, randomised trial to compare high-flux haemodialysis and high-dose haemodiafiltration, with the aim of clarifying which method is superior.

    At 61 centres in eight European countries, a total of 1,360 patients were randomised, with 683 treated with high-dose haemodiafiltration and 677 treated with high-flux haemodialysis three times a week.

    During a median follow-up of 30 months, all-cause mortality was 21.9% among those treated with high-flux haemodialysis, compared to 17.3% for those treated with high-volume haemodiafiltration. This 4.6% difference represents a 23% reduction in the risk of death.

    Lead investigator, Professor Peter Blankestijn (UMC Utrecht), said: “Our results show clear survival benefits for using haemodiafiltration over haemodialysis to treat kidney failure, akin to a 23% reduction in all-cause mortality. My hope is that haemodiafiltration can become the new standard.”

    Professor Matthias Rose (Charité University, Berlin), a senior author of the study and expert in patient-reported outcomes, said: “In addition to clinical events, patient perception and thus reported outcomes are very important.  We are currently performing in-depth analyses of the extensive data on patient-reported outcomes that have been collected in the CONVINCE study, with results expected later this year.”

    While haemodialysis is standard treatment in most countries, haemodiafiltration is less widely used in some places and is not used at all in places like the US. Most modern dialysis machines can perform either method, which would make a switch to haemodiafiltration relatively easy.

    Professor Andrew Davenport (UCL Medicine and the Royal Free Hospital), a senior author of the study, said: “During my career I’ve watched new treatments emerge for many diseases, from diabetes to cancer, but we haven’t seen the same advances in the treatment of chronic kidney disease. This study proves that targeting different molecules through haemodiafiltration has clear benefits for patients. I would say that this is the first major step forward in many years and is good news for kidney disease patients and their families.”

    The CONVINCE study was exclusively supported by the European Commission Research & Innovation, Horizon 2020, Call H2020-SC1-2016-2017 under the topic SC1-PM-10-2017: Comparing the effectiveness of existing healthcare interventions in the adult population (grant no 754803).

    [ad_2]

    University College London

    Source link

  • Think Twice Before Testing Your Hormones at Home

    Think Twice Before Testing Your Hormones at Home

    [ad_1]

    Across the internet, a biological scapegoat has emerged for almost any mysterious medical symptom affecting women. Struggling with chronic fatigue, hair loss, brain fog, or dwindling sex drive? When no obvious explanation is at hand, an out-of-whack endocrine system must be to blame. Women have too much cortisol, vloggers and influencers say; or not enough thyroxine, or the wrong ratio of progesterone to estradiol. Social media is brimming with advice from self-proclaimed hormone “gurus” and health coaches; the tag #hormoneimbalance has racked up a staggering 950 million views on TikTok alone.

    Now dozens of start-ups promise to diagnose these imbalances from the comfort of your home. All it takes is the prick of a finger, a urine sample, or a vial of spit. You mail your sample out to a lab or run the test right in your kitchen, no co-pay or doctor visit required. A few days later, you receive a slick lab report and in some cases, a customized treatment plan to alleviate the depression, the insomnia, the feeling of just being off.

    Hormone imbalances can indeed contribute to an array of mental and physical symptoms, and hormone testing overseen by providers is a routine practice in medicine. Doing so remotely could theoretically improve women’s health and access to care. But despite their growing popularity and Amazon-like convenience, at-home hormone tests might cause more problems than they solve. Several women’s-health and hormone specialists told me that remote testing has long been useful for detecting pregnancy and tracking ovulation, but that few, if any, products now for sale have been consistently and rigorously proven to work for broader, newly advertised purposes. Testing kits are marketed as a way of helping women decipher puzzling symptoms or assess their fertility. But experts said that the technology—at least as it stands right now—is unreliable and could have the opposite effect, causing anxiety and confusion instead.

    Mindy Christianson, an ob-gyn and the medical director of the Johns Hopkins Fertility Center, told me that in the best-case scenario, an accurate home hormone test would lead its users to seek out necessary medical care for real medical problems. That’s what happened to Chrissy Rice, a 38-year-old in Georgia. From 2018 to 2022, Rice experienced a racing heart, panic attacks, skin rashes, fatigue, and stomach pain—but her blood work and cardiac tests kept coming back normal. Her doctor chalked her symptoms up to anxiety and prescribed an anxiolytic medication. Rice wasn’t satisfied, so she skipped the meds and ordered a $249 women’s-health-testing kit from a company called Everlywell. The kit, which uses saliva and finger-prick sampling, claims to check for abnormal hormone levels that may be keeping women from “feeling their best.” When Rice’s results lit up with four abnormal readings, she was “honestly relieved,” she told me: It gave her confidence that her symptoms hadn’t all been in her head. When she brought the results to another provider, he ordered more tests and eventually diagnosed her with an autoimmune condition called Hashimoto’s, for which she’s since been treated.

    Read: No one really understands how to treat menopause

    Rice’s success story relied on a lot of things going right: The test correctly flagged that something about Rice’s body chemistry had gone awry. (In this case, #hormoneimbalance really did apply.) In response, Rice used her results to advocate for appropriate care from a trusted health provider. But not everyone is so lucky.

    Tests like the one Rice took rely on processes that have not yet been rigorously validated in clinical trials. Where traditional hormone testing involves in-person blood draws followed by a highly sensitive and specific process called liquid chromatography–tandem mass spectrometry, home tests typically use dried urine, dried blood, or saliva sampling and a variety of techniques for measuring what’s in those samples. Women have, of course, been peeing on pregnancy-testing sticks since the 1980s. But these tests work well because the target hormone is present at relatively high levels, and should be found only during pregnancy. By contrast, hormones such as estradiol, testosterone, and progesterone—which are commonly targeted by this new wave of start-ups’ tests—regularly circulate throughout the body during various stages of a woman’s life, and are far trickier to measure using the low-volume samples involved in dried urine, dried blood, and saliva tests.

    A handful of small studies from the past three decades (many of which are funded by direct-to-consumer testing companies or conducted by their employees) suggest that these methods may be accurate. Jennifer Conti, an ob-gyn physician and professor at the Stanford University School of Medicine who advises the home-hormone-testing start-up Modern Fertility, told me that the company’s internal data, especially a study published in the peer-reviewed journal Obstetrics & Gynecology in 2019, convinced her that its technology was useful for consumers who want to make more informed family-planning decisions. “But this idea that at-home testing is a godsend is not true,” Conti said. “It’s something that can be very helpful right now for a certain population of people to open the door and start a conversation.”

    Read: Can genetic counselors keep up with 23andMe?

    Other experts still aren’t confident that the tests are worthwhile. I asked Andrea Dunaif, a professor and specialist in endocrinology and women’s health at Mount Sinai, and Hershel Raff, an endocrinology and molecular-medicine expert at the Medical College of Wisconsin, to review the 2019 study. According to the study’s authors, their findings suggest that Modern Fertility’s finger-stick testing methods can be used interchangeably with traditional blood draws to measure fertility-related hormones. But Dunaif and Raff pointed out a laundry list of methodological issues that they argue limit the power of the findings: The type of assay used isn’t accurate for determining testosterone or estradiol levels in women. Researchers didn’t use appropriate hormone-level ranges to test accuracy. Samples were analyzed within 48 hours—a timeline that doesn’t match up with real-world shipping. (Current leadership and members of Modern Fertility’s clinical-research team declined multiple requests for comment. But Erin Burke, a clinical researcher who co-authored the study and is no longer working for Modern Fertility, said she stands by the data. She told me that the team’s work shows that these testing methods are accurate and precise.)

    Although many experts see minimal data to support their use, at-home tests can still be sold on account of a regulatory loophole: The FDA does not typically review what it calls “low risk general wellness” products before they hit the market. Some endocrinologists advise looking for home hormone tests with a certification from the Clinical Laboratory Improvement Amendments program (which is legally required for every direct-to-consumer testing company) or the College of American Pathologists, both of which ensure that a company’s labs maintain certain quality standards and undergo regular inspections. But Dunaif told me the certifications don’t guarantee precise results. She would never recommend that consumers use a currently available product for testing women’s sex steroid hormones remotely, she said, arguing that people will waste money and likely get information that is either “falsely reassuring or falsely distressing.” (Dunaif recently consulted for Quest Diagnostics, a large clinical-lab chain that doesn’t offer home hormone tests.)

    Charlotte, a New Jersey woman in her mid-30s, experienced the muddle of uncertain results firsthand. (I’m identifying her by only her first name to protect her medical privacy.) In 2021, Charlotte ordered a hormone panel from Modern Fertility after she began experiencing irregular periods. Her results showed an abnormally high level of prolactin, a hormone involved in ovulation and lactation, which made her think she might be infertile. Charlotte spent days scouring the internet for information while she waited to discuss the results with her doctor. When she finally showed her ob-gyn the Modern Fertility report, the doctor was incredulous. She basically dismissed the at-home results out of hand, and instead put Charlotte on progesterone. A few months later, Charlotte got pregnant.

    Read: Women aren’t just small men

    Like Rice’s home test, Charlotte’s helped her start a conversation with a trusted health-care provider and develop a plan. But Charlotte told me that the process wasn’t worth the panic-filled waiting game and desperate Googling. She wishes she’d skipped the home test and consulted her doctor first.

    Even when home hormone tests are accurate, their results are not diagnostic on their own. Drawing a straight line from hormone levels to a diagnosis is impossible without a medical history or physical exam; a user can’t predict her chances of pregnancy, for example, solely based on measurements of her fertility-related hormones. Nor would low levels of, say, estradiol or progesterone be enough to indicate endometriosis. Most people’s symptoms aren’t tied directly to a hormone imbalance, says Stephanie Faubion, the director of the Mayo Clinic Center for Women’s Health and the medical director of the North American Menopause Society. The more than 50 chemical messengers that coordinate all kinds of processes, including metabolism, reproduction, and mood, are constantly fluctuating and difficult to measure with a quick-hit hormone test, Faubion told me; people’s symptoms may be attributable to multiple interrelated factors. “Just checking a hormone level and saying Here’s your problem doesn’t serve women well,” she said. “It’s oversimplifying an issue.”

    Some companies offer physician-reviewed reports, chat services, or phone calls with health providers to clarify any confusion. But Mary Jane Minkin, a gynecologist, menopause expert, and clinical professor at Yale School of Medicine, told me that those services might not be enough to curb misinterpretation, especially if test results aren’t reliable. Minkin worried that users may make drastic lifestyle changes or take off-the-shelf supplements. Christianson, of the Johns Hopkins Fertility Center, said that a growing number of her patients visit her clinic believing they are infertile or in premature menopause based on abnormal readings, when it’s not true. Others are rushing to freeze their eggs unnecessarily. And Faubion worries that providers, too, might use tests that aren’t evidence-based to make decisions about hormone therapy for patients. Some testing start-ups already offer personalized treatment plans and bioidentical hormone-replacement therapy via telehealth based on a user’s results.

    Other experts had the opposite concern: that women whose home-test results appear normal would miss out on crucial interventions. Christianson told me that she’s seen men skip out on necessary infertility evaluations based on at-home semen tests. Women could end up making similar mistakes. And Dunaif said that women experiencing chronically irregular periods might be falsely reassured by a home hormone test and delay needed treatment for endocrine disorders or polycystic ovarian syndrome (PCOS).

    Read: When missed periods are a metabolic problem

    At-home-hormone-testing companies aim to solve a pressing demand for clarity and control as women address their medical needs. If women have been tempted to blame their hormones for anything that’s wrong, that’s at least partly because they aren’t receiving sufficient guidance from doctors. For decades, female patients have been dismissed, misdiagnosed, and mistreated by their health providers more than male patients have. Far less clinical research has been conducted on women than men, which can make health care a guessing game. A diagnosis for a hormone disorder such as PCOS or endometriosis typically takes consultations with several doctors across two to 10 years. Plus, traditional hormone testing can be expensive, and specialists are difficult to find. Only 1,700 reproductive endocrinologists and 2,000 menopause specialists practice in the United States; fertility clinics are rare outside cities.

    In an ideal world, women wouldn’t feel the need to circumvent their doctors to test their hormones at home. But as it stands, many are desperate for answers, and direct-to-consumer testing companies are responding to their frustrations. Someday, the tests might help point users to the appropriate specialist, provide useful information for women in medical deserts, or enable people to better monitor chronic conditions for which the relevant hormones are simple to measure. But until they are rigorously evaluated, women are left with imperfect choices.

    [ad_2]

    Ali Pattillo

    Source link

  • Metformin reduces long COVID risk

    Metformin reduces long COVID risk

    [ad_1]

    Newswise — MINNEAPOLIS/ST. PAUL (06/09/2023) — In a new study published in The Lancet Infectious Diseases, University of Minnesota researchers found that metformin, a drug commonly used to treat diabetes, prevents the development of long COVID. 

    The study, called COVID-OUT, investigated if early outpatient COVID-19 treatment with metformin, ivermectin or fluvoxamine could prevent long COVID. Long COVID is a chronic illness that can affect up to 10% of people who have had COVID-19. 

    “The results of this study are important because long COVID can have a significant impact on people’s lives,” said Carolyn Bramante, MD, principal investigator and an assistant professor at the U of M Medical School. “Metformin is an inexpensive, safe and widely available drug, and its use as a preventive measure could have significant public health implications.”

    This was a large, placebo-controlled randomized clinical trial which enrolled volunteers across the United States. The study found: 

    • Those who received metformin were more than 40% less likely to develop long COVID than those who received an identical looking placebo. 
    • For participants who started metformin less than four days after their COVID symptoms started, metformin decreased the risk of long COVID by 63%. 
    • The effect was consistent across different demographic populations of volunteers who participated and across multiple viral variants, including the Omicron variant. 
    • Ivermectin and fluvoxamine did not prevent long COVID.

    The study included more than 1,200 participants who were randomly chosen to receive either metformin or placebo, and an additional subset received ivermectin, fluvoxamine or their placebos. Participants were between 30 and 85 years old who qualified as overweight or obese. Over 1,100 of the participants reported on their symptoms for up to 10 months after their initial COVID-19 diagnosis. 

    “This long-term outcome from a randomized trial is high-quality evidence that metformin prevents harm from the SARS-CoV-2 virus,” said Dr. Bramante, who is also an internist and pediatrician with M Health Fairview. “While half of our trial had been vaccinated, none had been previously infected with the COVID-19 virus. Further research could show whether it is also effective in those with previous infection or in adults with lower body mass index.” 

    Metformin’s ability to stop the virus was predicted by a simulator developed by U of M Medical School and College of Science and Engineering Biomedical Engineering faculty. The model has been highly accurate to date, successfully predicting, among others, the failure of hydroxychloroquine and the success of remdesivir before the results of clinical trials testing these therapies were announced.

    Funding was provided by the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants and the United Health Foundation.This research was also supported by the National Institutes of Health’s National Center for Advancing Translational Sciences under award number [UL1TR002494, KL2TR002492, and UM1TR004406]. 

    -30-

    The University of Minnesota Medical School, School of Public Health, College of Science and Engineering and M Health Fairview served as the lead site. The trial was also conducted at Northwestern University; University of Colorado, Denver; Olive View – UCLA Education & Research Institute in Los Angeles; Optum Health, and with scientific collaboration from partners at the University of North Carolina at Chapel Hill, Vanderbilt University, and Emory University School of Medicine. 

    The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.

    About the University of Minnesota Medical School
    The University of Minnesota Medical School is at the forefront of learning and discovery, transforming medical care and educating the next generation of physicians. Our graduates and faculty produce high-impact biomedical research and advance the practice of medicine. We acknowledge that the U of M Medical School, both the Twin Cities campus and Duluth campus, is located on traditional, ancestral and contemporary lands of the Dakota and the Ojibwe, and scores of other Indigenous people, and we affirm our commitment to tribal communities and their sovereignty as we seek to improve and strengthen our relations with tribal nations. For more information about the U of M Medical School, please visit med.umn.edu.

    [ad_2]

    University of Minnesota Medical School

    Source link

  • Treatment decisions in new era of individualized therapy for metastatic hormone-sensitive prostate cancer guided by Dana-Farber case study

    Treatment decisions in new era of individualized therapy for metastatic hormone-sensitive prostate cancer guided by Dana-Farber case study

    [ad_1]

    RESEARCH SUMMARY

    Study Title: Early Treatment Intensification in Metastatic Hormone-Sensitive Prostate Cancer

    Publication: Journal of Clinical Oncology

    Dana-Farber Cancer Institute authors: Jeremiah Wala; MD, PhD, Paul Nguyen, MD, MBA; Mark Pomerantz, MD

    Summary: Oncologists have traditionally prescribed androgen deprivation therapy (ADT) alone for patients with metastatic hormone-sensitive prostate cancer (mHSPC).

    Newswise — Now there are many possible treatment options. Clinical trials have shown that more aggressive up-front treatment with a range of combination therapies improves outcomes. This case study shows how Dana-Farber Cancer Institute oncologists interpreted the evidence from these trials and applied it to an individual patient with mHSPC.

    The researchers recommend aggressive up-front treatment with triplet therapy (ADT, an androgen-receptor pathway inhibitor, and chemotherapy) for patients who can tolerate chemotherapy, and especially for patients with high-volume disease. For patients with low-volume disease, they recommend adding radiation therapy if feasible. The researchers also recommend the use of PSMA-PET scans to find metastases, evaluate treatment response, and identify potential sites for radiation.

    Impact: Choosing a treatment approach requires interpretation of the results of many trials and the consideration of multiple factors unique to each patient. This case study provides that interpretation and gives evidence-based guidance for how to navigate decision-making for individual patients. 

    Funding: This study was funded by the National Cancer Institute. 

    # # #

     

    [ad_2]

    Dana-Farber Cancer Institute

    Source link

  • MEDSIR Study Finds No Progression-Free Survival Benefit with Palbociclib Maintenance After First-Line Regimen in HR+/HER2- Advanced Breast Cancer Patients

    MEDSIR Study Finds No Progression-Free Survival Benefit with Palbociclib Maintenance After First-Line Regimen in HR+/HER2- Advanced Breast Cancer Patients

    [ad_1]

    Newswise — JERSEY CITY, N.J., June 5, 2023 /PRNewswire/ — MEDSIR announced today the results of the PALMIRA trial. This randomized phase 2 study evaluated the safety and efficacy of palbociclib maintenance in combination with second-line endocrine therapy in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer who had showed a confirmed progressive disease on first-line palbociclib plus endocrine therapy-based treatment after having achieved clinical benefit to this regimen. The results of this trial demonstrate that palbociclib maintenance does not significantly improve progression-free survival, the primary endpoint of the study, compared with second-line endocrine therapy alone in this patient population.

    MEDSIR Study Finds No Progression-Free Survival Benefit with Palbociclib Maintenance After First-Line Regimen in HR+/HER

    The PALMIRA study is sponsored by MEDSIR, a company dedicated to advancing clinical research in oncology, and was led by Dr. Antonio Llombart-Cussac along with Dr. Javier Cortés and Dr. José Pérez as Scientific Coordinators. The trial involved 198 patients with HR+/HER2- advanced breast cancer from 41 centers in 6 European countries.

    Endocrine therapy is the mainstay of treatment for patients with HR+/HER2- advanced breast cancer. Several studies have demonstrated that the addition of cyclin-dependent kinases 4 and 6 (CDK4/6) to first- and second-line endocrine therapy leads to an improved progression-free survival and overall survival. However, the optimal treatment after progression on a CDK4/6 inhibitor in patients with HR+/HER2- advanced breast cancer remains undetermined.

    One of the therapeutic options that have been evaluated in this scenario is the maintenance of CDK4/6 inhibition beyond progression switching the endocrine therapy and maintaining or shifting the CDK4/6 inhibitor or continuing the same endocrine therapy and changing to a different CDK4/6 inhibitor. Some of these studies had already suggested a continued benefit from this clinical approach but they must be interpreted with caution due to potential biases, mainly the use of a different CDK4/6 inhibitor.

    The PALMIRA study aimed to determine if palbociclib maintenance could improve the antitumor activity of second-line endocrine therapy in HR+/HER2- advanced breast cancer patients who had showed a confirmed progressive disease on first-line palbociclib plus endocrine therapy-based treatment after having achieved clinical benefit to this regimen.

    “Results of the PALMIRA trial, while negative, will guide further research on the optimal treatment upon progression to CDK4/6 inhibitors and our clinical practice,” said Dr. Llombart-Cussac, principal investigator of the study and Head of Service at Arnau de Vilanova Hospital in Valencia, Spain. Findings from the PALMIRA study indicate that “re-treatment with the same CDK4/6 inhibitor and switching the endocrine therapy does not improve patient outcomes”.

    Dr. Cortés, director of the International Breast Cancer Center, stated, “based on the results of the PALMIRA study, we suspect that there is a subgroup of patients that could benefit from maintaining palbociclib after prior progression on a palbociclib-based regimen. Biomarkers are the way to identify these patients and optimize the best future treatment options for them”. 

    The results of the primary endpoint, progression-free survival, have been presented as an oral presentation at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

    ABOUT MEDSIR
    Founded in 2012, MEDSIR works closely with its partners to drive innovation in oncology research. Based in Spain and the United States, the company manages all aspects of clinical trials, from study design to publication, utilizing a global network of experts and integrated technology to streamline the process. The company offers proof-of-concept support and a strategic approach that helps research partners experience the best of both worlds from industry-based clinical research and investigator-driven trials. To promote independent cancer research worldwide, MEDSIR has a strategic alliance with Oncoclínicas, the leading oncology group in Brazil with the greatest research potential in South America. Learn how MEDSIR brings ideas to life: www.medsir.org 

    [ad_2]

    Medica Scientia Innovation Research (MEDSIR)

    Source link

  • MEDSIR’s PHERGain Trial Shows Potential for Chemotherapy-free Treatment of HER2-positive Early Breast Cancer

    MEDSIR’s PHERGain Trial Shows Potential for Chemotherapy-free Treatment of HER2-positive Early Breast Cancer

    [ad_1]

    Newswise — JERSEY CITY, N.J., June 2, 2023 /PRNewswire/ — MEDSIR announced today the positive results of the PHERGain trial. This study is the first to use an adaptive design that tailors treatment in the neoadjuvant/adjuvant setting of patients with HER2-positive early breast cancer. The main objective of this trial was to assess the feasibility of a chemotherapy-free strategy based on a dual HER2 blockade with trastuzumab and pertuzumab through a positron emission tomography (PET)-based, pathologic complete response response(pCR)-adapted strategy.

    MEDSIR PHERGain trial is the first to use an adaptive design in HER2-positive early breast cancer. 

    PHERGain is a randomized, controlled phase 2 clinical trial that involved 356 early-stage HER2-positive breast cancer patients from 45 centers in seven European countries. It was sponsored by MEDSIR, a company dedicated to advancing clinical research in oncology, and led by scientific investigators Dr. Javier Cortés, Dr. Antonio Llombart-Cussac, and Dr. José Pérez. The first primary endpoint was the pCR rate in patients with PET response included in group B, whose positive results were published in 2021 in Lancet Oncology.

    The results of the second primary endpoint, 3-year invasive disease-free survival in all patients assigned to group B, have been presented at the 2023 American Society of Clinical Oncology (ASCO) congress. Overall, 95.4% of patients who followed this chemotherapy de-escalation strategy using PHERGain’s adaptive design remained cancer-free after three years of follow-up from breast cancer surgery. This is especially relevant because around 30% of these patients did not receive chemotherapy without compromising patient’s outcome. Among this latter group, 98.9% remained cancer-free after three years of follow-up from breast cancer surgery.

    “This study offers a potential future therapeutic option that enables a significant reduction of toxicity and an improvement in quality of life for this patient population without reducing efficacy”, explains Dr. Cortés. In addition, the most relevant finding “is that 99% of the subgroup who received anti-HER2 therapy without chemotherapy have not presented a recurrence of the disease after three years of follow-up”.

    “These results bring us closer to the end of chemotherapy in a significant percentage of patients with this type of tumor,” explains Dr. Llombart-Cussac, “It is critical to design more efficient strategy-based clinical trials with adaptive designs to bring effective therapies to patients in the shortest amount of time.”

    ABOUT MEDSIR

    Founded in 2012, MEDSIR works closely with its partners to drive innovation in oncology research. Based in Spain and the United States, the company manages all aspects of clinical trials, from study design to publication, utilizing a global network of experts and integrated technology to streamline the process. The company offers proof-of-concept support and a strategic approach that helps research partners experience the best of both worlds from industry-based clinical research and investigator-driven trials. To promote independent cancer research worldwide, MEDSIR has a strategic alliance with Oncoclínicas, the leading oncology group in Brazil with the greatest research potential in South America. Learn how MEDSIR brings ideas to life: www.medsir.org

    [ad_2]

    Medica Scientia Innovation Research (MEDSIR)

    Source link

  • ASCO: Targeted therapy induces responses in HER2-amplified biliary tract cancer

    ASCO: Targeted therapy induces responses in HER2-amplified biliary tract cancer

    [ad_1]

    ABSTRACT: 4008

    Newswise — CHICAGO ― HER2-targeted bispecific antibody zanidatamab demonstrated durable responses in patients with treatment-refractory HER2-positive biliary tract cancer (BTC), researchers from The University of Texas MD Anderson Cancer Center reported at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. The study results also were published today in The Lancet Oncology.

    In the first cohort of the global Phase II HERIZON-BTC-01 trial, which included 80 patients with HER2-positive tumors, the confirmed objective response rate (cORR) was 41% with a median duration of response (DOR) of 12.9 months at a median follow-up of 12.4 months. Among the 33 responders, 49% had ongoing responses and 82% had a response lasting more than 16 weeks. This is the largest study of a HER2-targeted drug in BTC.

    “Chemotherapy for patients with biliary tract cancers who have progressed on first-line therapy is usually associated with a 5% response rate,” said global trial lead Shubham Pant, M.D., professor of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics. “These results provide evidence that zanidatamab can achieve durable responses and may offer a new treatment opportunity for patients who previously had limited options.”

    Patients with advanced BTC who progress after first-line treatment are offered standard-of-care therapies with limited clinical benefit and only modest improvement in survival. HER2-targeted therapies have improved survival in HER2-positive breast and gastric cancers, but there currently is no approved HER2-targeted therapy for BTC.

    Zanidatamab was first evaluated in a Phase I trial led by Funda Meric-Bernstam, M.D., chair of Investigational Cancer Therapeutics. The trial results supported HER2 as an actionable target in various cancer types, including biliary tract cancer. Based on those results, MD Anderson researchers advanced zanidatamab into this Phase II trial for patients with BTC.

    Biliary tract cancer, also known as cholangiocarcinoma, develops in the bile ducts, a series of thin tubes that run from the liver to the small intestine. There are three different types of BTC, whose names are based on the location where the cancer forms. According to the American Cancer Society, around 8,000 people in the U.S. are diagnosed each year with BTC. However, the true count likely is higher because these cancers can be hard to diagnose and are often misclassified, Pant explained. The five-year survival rate for metastatic BTC is less than 5%, highlighting an urgent need for new treatments.

    This open-label, single-arm trial evaluated the anti-tumor activity of zanidatamab in patients with HER2-amplified advanced BTC, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer. The trial was conducted at 67 sites; patients were divided into two cohorts based on HER2 expression (positive or low/negative) by tumor immunohistochemistry. The primary endpoint was cORR in the HER2-positive cohort.

    The study enrolled 80 patients in the HER2-positive cohort and seven patients in the HER2-low/negative cohort. All patients had received one previous line of gemcitabine-containing therapy. The median age was 64 years and patients were 65.5% Asian, 28.7% white and 5.7% other. Of the trial participants, 52% had gallbladder cancer, 30% had intrahepatic cholangiocarcinoma, and 18% had extrahepatic cholangiocarcinoma.

    There were no responses to zanidatamab observed in the HER2-low/negative cohort. Across both cohorts, grade 3 treatment-related adverse events occurred in 18% of patients. Two patients (2.3%) discontinued zanidatamab due to an adverse event. No grade 4 or 5 treatment-related adverse events were reported.

    “Given this data, we believe strongly that there should be continued efforts to explore zanidatamab as a viable treatment option for HER2-positive biliary tract cancer,” Pant said. “We are encouraged by the potential impact of zanidatamab on improving patient outcomes.”

    Pant and his team still are evaluating progression-free survival and overall survival in these patients. Additionally, clinical trials are underway to further investigate the therapeutic potential of zanidatamab as a monotherapy and in combination with first-line chemotherapy for HER2-positive BTC.

    This study was funded by Zymeworks BC Inc. and BeiGene Ltd. Pant has worked in a consulting/advisory role for and received research support from Zymeworks. A full list of co-authors and their disclosures can be found here.

    – 30 –

    [ad_2]

    University of Texas MD Anderson Cancer Center

    Source link

  • Promising Phase III Results Give Hope to People Living with Myelodysplastic Syndromes

    Promising Phase III Results Give Hope to People Living with Myelodysplastic Syndromes

    [ad_1]

    Newswise — Amer Zeidan, MBBS, medical director of the hematology early therapeutics research program at Yale Cancer Center and associate professor of medicine (hematology) at Yale School of Medicine, will reveal new data at the American Society of Clinical Oncology (ASCO) annual meeting from a phase III study evaluating the efficacy of imetelstat in red blood cell (RBC) transfusion-dependent lower-risk myelodysplastic syndrome (LR-MDS) patients. Myelodysplastic syndromes(MDS) are a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. The study results demonstrate significant and clinically meaningful efficacy, representing a potential breakthrough in the treatment of anemic LR-MDS.

    Imetelstat, a telomerase inhibitor, was evaluated in patients who were heavily RBC transfusion-dependent LR-MDS and who were refractory or ineligible for erythropoiesis-stimulating agents (ESAs), but did not receive lenalidomide or hypomethylating agents (other drugs used to treat MDS). The phase III study, known as IMerge, enrolled a total of 178 patients. The findings from the study provide critical evidence supporting imetelstat’s efficacy and safety profile. These results are expected to have a substantial impact on future treatment strategies for patients diagnosed with LR-MDS.

    Dr. Zeidan, first and presenting author of the research at ASCO, answered questions on the study and its significance for patients living with MDS:

    Q: What is the significance of this study?

    A: “This is a very important study. Imetelstat is a first-in-class agent. It’s a first-in-class telomerase inhibitor, and this is the first time we have a phase III study of a drug in this class. We already completed the phase II study that was single arm that looked at a similar population of patients with lower risk MDS (myelodysplastic syndromes) who are heavily transfusion dependent, and the transfusion independence rate with the drug was around 40%. Transfusions in MDS are associated with increased risk of complications, increased risk of death, not to mention healthcare utilization and costs. So, trying to reduce transfusions and ideally make patients transfusion independent is a very important goal of treatment in patients with lower risk MDS.

    So the excellent activity of imetelstat in the phase II part of the study was taken to a phase III trial and what we have found in this study is what we actually expected based on the phase II trial: the transfusion dependence rate was much better with imetelstat compared to placebo, it was around 40% for an eight-week duration of transfusion dependence, the primary endpoint of the study, compared to 15% with a placebo; and most importantly, it was also durable. The median duration of transfusion independence for those who responded was more than 50 weeks. So clearly, a very positive study, very consistent with the phase II data. I think this drug could become an important option for patients.”

    Q: What are the key findings from the data? What will you highlight at ASCO?

    A: “During the ASCO presentation, we’ll discuss in detail, the efficacy of the drug in terms of transfusion independence, hematologic improvement, durability of response, but also looking within subgroups for patients based on the genetic profile. We will also discuss early signs of disease modification that we are seeing through reduction of variable allele frequency of important mutations that contribute to the pathogenesis of MDS. We’ll also discuss the side effect profile and how the interruption of therapy has led to, I think, a manageable and reversible side-effect profile, mostly in the setting of liver enzyme abnormalities and cytopenias (a medical condition where there are a low number of red blood cells).”

    Q: Are there other treatment options for this niche group of patients affected by this cancer?

    A: “Yes, so myelodysplastic syndromes have been renamed neoplasms by the World Health Organization, the most recent classification to emphasize that it’s a cancer. Many people think of MDS as an anemia or a pre-leukemia or a syndrome, but they are actually cancers. However, they differ in their severity. Patients in general are grouped into two big groups, lower risk and higher risk. In lower risk patients, those patients can live for years, but they have a lot of complications related to the low blood counts. That could be anemia, thrombocytopenia, or neutropenia, or a combination of these, but the most common use cytopenia is anemia. Anemia often is associated with reduced quality of life. The patient often needs regular transfusions. It’s also associated with significant complications and high risk of death, as well as issues related to needing to go to the clinic frequently, healthcare utilization costs. Correction of anemia is very important. Historically, the only treatment we had was erythropoiesis stimulating agents for patients with lower risk MDS. In recent years, other drugs have been approved like lenalidomide, as well as hypomethylating agents and luspatercept. However, the response to these drugs is limited, and at some point, the patient will progress and will need additional treatment. I think imetelstat potentially could fill a very important gap there because those patients are generally not going to be cured without a bone marrow transplant, which is not something that’s commonly done in MDS patients where the average age is in the early 70s. The goal is to try to improve quality of life in those lower risk MDS patients and make them transfusion independent as much as possible and that’s generally achieved by sequential therapy. So you go from one agent to the next, while trying to maintain quality of life keeping the patient out of the hospital and minimizing complications of the treatment itself.”

    Q: What is next in terms of research. What would you like done in future studies?

    A: “This is a very important question. I think the next step is going to be focusing more on how to increase the overall durability of response as well as increased the rate of response. And I think that’s going to be done by combining drugs. We have several active drugs now. So, figuring out how to combine them, and probably trying to treat patients earlier in their disease course will be important, so they don’t even get to the point of becoming transfusion dependent. Several of those studies I think are going to happen over the next few years. And of course, there are other drugs that are being studied in phase I and phase II trials. Some of those hopefully will also lead to benefit to patients so that if we cannot cure the disease, we can for most patients at least improve their quality of life, make transfusions as least as possible, and also make sure they are out of the hospital and having a good quality of life.”

    Q: What does the presentation at ASCO mean to you?

    A: “It’s one of the most gratifying moments for a clinical investigator when we hear a trial we worked on is positive. The reason why we do clinical trials is to help our patients. So have a positive trial and especially with an agent that you have worked on for years, and you have been very involved in the trial for a long time, not only in accruing patients, but also in the design and the conduct and oversight of the study and to have a trial being positive, especially for a randomized phase III trial, is a very good feeling, and the day when you hear that the results are positive is a day that you tend to remember for a very long time because what you have worked on did not only help your own patients, but hopefully if the drug gets approved, it’s going to help many patients that you have not directly interacted with, which is I think is the most important mission of any clinical research. We are the face of the trial as clinical investigators, but we have a huge team here at Yale. A lot of coordinators, clinical research nurses, regulatory staff, and our nurse practitioners – all of them have been very important to the conduct of the trial here at Yale. This was a global study that happened in many countries, many centers, and it’s a coordinated effort. So we are presenting the data on behalf of everybody and hoping that the regulatory review will be successful, and we have another option for our patients.”

    [ad_2]

    Yale Cancer Center/Smilow Cancer Hospital

    Source link

  • Women with breast cancer shed pounds thanks to telephone-based weight loss program, clinical trial finds

    Women with breast cancer shed pounds thanks to telephone-based weight loss program, clinical trial finds

    [ad_1]

    Newswise — Boston – Women with obesity when they are diagnosed with early breast cancer have a higher risk of recurrence or a second cancer compared to women whose weight is in the normal range and it can be hard to lose weight after being diagnosed with breast cancer. Now, a clinical trial has shown that a telephone-based weight loss program can help patients with breast cancer whose body mass index is in the overweight or obese range lower their weight by a meaningful degree.

    The findings, to be reported by Dana-Farber Cancer Institute investigators at the American Society of Clinical Oncology (ASCO) Annual Meeting, set the stage for follow-up research into whether this type of program can extend patients’ survival and lower their risk of a breast cancer recurrence.

    “We know that women with obesity when they are diagnosed with breast cancer have a higher risk of dying of the disease, of developing second cancers, and of dying from any cause,” says Dana-Farber’s Jennifer Ligibel, MD, the principal investigator of the trial, who will present the findings at ASCO. “But we don’t know whether helping patients lose weight after diagnosis will improve treatment outcomes. That’s what this study seeks to discover.”

    The Breast Cancer Weight Loss (BWEL) trial, a Phase III trial supported by the National Cancer Institute, enrolled nearly 3,200 women from more than 600 cancer treatment centers in the U.S. and Canada. The participants, who had been diagnosed with stage 2 or 3 HER2-negative breast cancer, had completed chemotherapy and radiation therapy (if it was to be administered) and were randomly assigned to receive either a telephone-based weight-loss program plus health education or health education alone. The weight-loss program, conducted by phone, coached patients in reducing their calorie intake and increasing exercise.

    Participants’ height and weight were measured when they entered the study and 12 months later. At the 12-month mark, researchers checked the weight of nearly 2,400 patients who were free of breast cancer.

    “We found the weight-loss program was highly successful in helping patients lower their weight,” Ligibel says.  Women who received the telephone-based intervention lost an average of 4.8% of their baseline body weight, compared to an average 0.9% increase in body weight among those in the control group.

    The findings were especially noteworthy in that they were consistent regardless of patients’ age, race, ethnicity, socioeconomic status, and education level, and type of breast cancer they had.

    Within this overall trend, however, researchers noticed some differences in patterns of weight change among the participants. While the weight-loss program was effective in both older and younger patients, younger women experienced a somewhat smaller weight loss. Younger women who didn’t receive weight-loss coaching gained a bit more weight than older participants, so the amount of weight change was relatively similar in older and younger patients.

    A similar pattern occurred among Black patients, who made up 13% of trial participants. Black women in the weight-loss program group lost less weight, on average, than others but Black women in the control group gained more weight than control participants of other races and ethnicities. However, women in the weight loss program lost more weight than women in the control group, regardless of their age, race, ethnicity, or other characteristics.

    The results provide a lead-in to the next phase of the study. “We’ll continue to follow patients who enrolled in the BWEL trial to determine whether the weight-loss program reduces the risk of cancer recurrence and cancer-related mortality,” Ligibel remarks. “We hope this research ultimately shows that healthy lifestyle change after a cancer diagnosis has a positive impact on outcomes, so we’ll be able to routinely offer this type of program to patients as a part of their breast cancer care.”

    Ligibel will present results from the BWEL trial during the Oral Abstract Session on Symptoms and Survivorship (Abstract 12001) during ASCO in Chicago on June 5, 2023, 9:12am ET.

    About Dana-Farber Cancer Institute 

    Dana-Farber Cancer Institute is one of the world’s leading centers of cancer research and treatment. Dana-Farber’s mission is to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. We provide the latest treatments in cancer for adults through Dana-Farber Brigham Cancer Center and for children through Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Dana-Farber is the only hospital nationwide with a top 5 U.S. News & World Report Best Cancer Hospital ranking in both adult and pediatric care.

    As a global leader in oncology, Dana-Farber is dedicated to a unique and equal balance between cancer research and care, translating the results of discovery into new treatments for patients locally and around the world, offering more than 1,100 clinical trials. 

    ###

    [ad_2]

    Dana-Farber Cancer Institute

    Source link

  • Biomarkers may help ID treatment of acute kidney injury

    Biomarkers may help ID treatment of acute kidney injury

    [ad_1]

    Newswise — Hospital inpatients who develop an acute kidney injury (AKI) generally fare poorly after being discharged, and have few options for effective treatment.  

    A UW Medicine-led study published recently in American Journal of Kidney Diseases suggests that new tests might improve this narrative.

    In the study, “about 30% of the patients that came into the hospital developed AKI, which means in a matter of hours or days, their kidneys might be failing because of reaction to drugs or contracting sepsis,” said lead author Dr. Pavan Bhatraju, an assistant professor of pulmonary and critical care medicine at the University of Washington School of Medicine.

    Causes of AKI vary. For instance, sepsis, medication and inadequate blood supply in someone who is undergoing cardiac bypass are all potential causes of kidney injury. It’s also the case that, within the kidneys, different cell types can be injured in the process of AKI, said Dr. Jonathan Himmelfarb, a professor of nephrology at the UW School of Medicine and the study’s senior author.

    “The way that we diagnose acute kidney injury today relies on a simple blood test of kidney function or a change in urine output,” Himmelfarb said. “These relatively crude diagnostic tools don’t detect the specific cause of injury or predict which individuals will be more likely to respond to a treatment or recover kidney function.”

    Unfortunately, effective medical therapies do not exist for this population of patients, Bhatraju said. In their paper, the investigators proposed a way to classify subpopulations of AKI patients with the aim of identifying therapies specific patient populations.  

    In much the same way that distinct biomarkers inform treatments of subgroups of patients with cancer or asthma, so, too, could blood- and urine-based biomarkers help identify subgroups of patients with AKI, leading to new ideas for treatments, the authors said.

    In the study, the researchers retrospectively analyzed 769 patients with AKI and 769 without the condition, and followed them for five years after hospital discharge. The researchers found two molecularly distinct AKI subgroups, or sub-phenotypes, that were associated with differing risk profiles and long-term outcomes.

    Patients in one group had higher rates of congestive heart failure, while another group had higher rates of chronic kidney disease and sepsis, Bhatraju said. The patients in the second group also had a 40% higher risk for major adverse kidney events five years later, compared with the first group, he said.

    Interestingly, Bhatraju added, age, sex, diabetes rate or major surgical procedure as the cause of AKI was not different across AKI subgroups. This finding suggests that commonly measured clinical factors may not predict the AKI subgroups, and that identification requires measurement of blood and urine biomarkers, he said.

    “We’re attempting to better understand the clinical factors and molecular drivers of acute kidney injury so that, in the long run, we can better treat the different ways that people experience this disease process,” Himmelfarb added. “We want to better understand the individual characteristics of people who get acute kidney injury so we can establish common characteristics of subgroup populations of these patients to know whose risk is relatively higher or lower, and work toward treatments specific to their needs.

    “Our paper is one step on the path to tailoring clinical trials of new therapies to the people who are most likely to respond to those therapies,” Himmelfarb said.  

    This study was supported by the supplemental American Recovery and Reinvestment Act funds through the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health (grants U01DK082223, U01DK082185, U01DK082192, U01DK082183, U01DK084012 and R01DK098233) and by the NIH (K23DK116967, R01DK133177, U2CDK114886, UG3TR002158, and U01DK099923).

    [ad_2]

    University of Washington School of Medicine and UW Medicine

    Source link

  • In newly released study findings, University of Miami cardiologists found that high BMI patients who lost 3% or more of their body weight prior to ablation saw greater freedom from AF post-ablation

    In newly released study findings, University of Miami cardiologists found that high BMI patients who lost 3% or more of their body weight prior to ablation saw greater freedom from AF post-ablation

    [ad_1]

    Weight Loss Before Afib Ablation Procedure Results in Improved Outcomes Among Obese Patients

    Results from a new clinical trial found overweight and obese patients with persistent and paroxysmal atrial fibrillation (AF) who lose weight prior to a catheter ablation procedure have improved clinical outcomes. The study, led by researchers with UHealth – the University of Miami Health System and the Miller School of Medicine, identifies weight loss before undergoing an ablation procedure as a risk-factor reduction tool for AF patients. Findings were presented today as a late-breaking clinical trial during Heart Rhythm 2023. 

    Read more: https://www.newswise.com/articles/weight-loss-before-afib-ablation-procedure-results-in-improved-outcomes-among-obese-patients?ta=home 

    Expert: Jeffrey Goldberger, M.D., M.B.A, Director, Center for Atrial Fibrillation, Professor of Medicine & Biomedical Engineering at UHealth – the University of Miami health System and the Miami Miller School of Medicine.

    Quote: 

    “We are constantly evolving our approach to AF to identify new ways to prevent recurrence and improve long term outcomes. While we already know the impact weight can have on overall outcomes, we believe the magnitude of the effect during this study is quite striking and that the findings show that even moderate weight loss may lead to a positive effect, but further analysis incorporating the potential independent contribution of Liraglutide is necessary” said Dr. Goldberger. “We hope that our findings will encourage physicians to integrate weight loss and risk factor modification into their treatment plans for patients undergoing catheter ablation and drive even more research dedicated to finding additional supportive solutions for patients living with AF.”

    [ad_2]

    University of Miami Health System, Miller School of Medicine

    Source link

  • Weight Loss Before Afib Ablation Procedure Results in Improved Outcomes Among Obese Patients

    Weight Loss Before Afib Ablation Procedure Results in Improved Outcomes Among Obese Patients

    [ad_1]

    Newswise — Results from a new clinical trial found overweight and obese patients with persistent and paroxysmal atrial fibrillation (AF) who lose weight prior to a catheter ablation procedure have improved clinical outcomes. The study, led by researchers with UHealth – the University of Miami Health System and the Miller School of Medicine, identifies weight loss before undergoing an ablation procedure as a risk-factor reduction tool for AF patients. Findings were presented today as a late-breaking clinical trial during Heart Rhythm 2023. 

    AF is the most common type of arrhythmia. There are approximately 2.3 million people in the United States who have AF, with 160,000 new cases diagnosed every year. Catheter ablation is a frequently used treatment for people with arrhythmias that can’t be controlled by medication or with certain types of arrhythmias from the heart’s upper chambers.1 While catheter ablation is a common AF treatment option, researchers are continuously evaluating how to improve AF ablation patient outcomes. This trial sought to determine whether additional non-ablation therapy targets can be integrated into treatment plans for patients undergoing catheter ablation for persistent AF and paroxysmal AF. 

    In the study, 65 patients with BMI≥27 kg/m2 who opted for catheter ablation to treat AF were enrolled and randomized to a 3-month pre-ablation period of standard risk factor modification (RFM) or RFM plus Liraglutide. From the enrolled participants, there were 59 patients (age 62±9 years, 27% female) weighing 106.4±18.5 kg (BMI 36.1±5.8 kg/m2); 79% had persistent AF and 21% had paroxysmal AF with 85% having hypertension, 27% diabetes, and 44% obstructive sleep apnea. Patients with a <3% weight change prior to their ablation procedure were labeled as Group 1 and patients with a ≥3-10% weight change were classified as Group 2. 

    The results showed AF status from enrollment to 6 months post-ablation. Group 1 had 29 patients with 0.2±2.7% weight gain and Group 2 had 30 patients with 5.6±1.8% weight loss. Freedom from AF off antiarrhythmic drugs at 6 months was 61% in Group 1 versus 88% in Group 2 (Fisher’s Test p=0.046, OLR p=0.0431). For patients with persistent AF treated with ablation (including one whose AF resolved with weight loss), freedom from AF off antiarrhythmic drugs at 6 months was 61% in Group 1 versus 90% in Group 2 (Fisher’s Test p=0.058, OLR p=0.051) and at 12 months was 42% in Group 1 versus 81% in Group 2 (Fisher’s Test p=0.050, OLR p=0.038). 1 Catheter ablation. Catheter Ablation | Johns Hopkins Medicine. (2021, February 22) 

    “We are constantly evolving our approach to AF to identify new ways to prevent recurrence and improve long term outcomes. While we already know the impact weight can have on overall outcomes, we believe the magnitude of the effect during this study is quite striking and that the findings show that even moderate weight loss may lead to a positive effect, but further analysis incorporating the potential independent contribution of Liraglutide is necessary” said Jeffrey Goldberger, M.D., M.B.A, Director, Center for Atrial Fibrillation, Professor of Medicine & Biomedical Engineering at UHealth – the University of Miami health System and the Miami Miller School of Medicine. “We hope that our findings will encourage physicians to integrate weight loss and risk factor modification into their treatment plans for patients undergoing catheter ablation and drive even more research dedicated to finding additional supportive solutions for patients living with AF.” 

    The authors of this trial would like to see additional trials focused on assessing the role of weight and weight loss in improving AF ablation outcomes and potentially identifying novel procedural approaches.

    [ad_2]

    University of Miami Health System, Miller School of Medicine

    Source link

  • Did Scientists Accidentally Invent an Anti-addiction Drug?

    Did Scientists Accidentally Invent an Anti-addiction Drug?

    [ad_1]

    This article was featured in One Story to Read Today, a newsletter in which our editors recommend a single must-read from The Atlantic, Monday through Friday. Sign up for it here.

    All her life, Victoria Rutledge thought of herself as someone with an addictive personality. Her first addiction was alcohol. After she got sober in her early 30s, she replaced drinking with food and shopping, which she thought about constantly. She would spend $500 on organic groceries, only to have them go bad in her fridge. “I couldn’t stop from going to that extreme,” she told me. When she ran errands at Target, she would impulsively throw extra things—candles, makeup, skin-care products—into her cart.

    Earlier this year, she began taking semaglutide, also known as Wegovy, after being prescribed the drug for weight loss. (Colloquially, it is often referred to as Ozempic, though that is technically just the brand name for semaglutide that is marketed for diabetes treatment.) Her food thoughts quieted down. She lost weight. But most surprisingly, she walked out of Target one day and realized her cart contained only the four things she came to buy. “I’ve never done that before,” she said. The desire to shop had slipped away. The desire to drink, extinguished once, did not rush in as a replacement either. For the first time—perhaps the first time in her whole life—all of her cravings and impulses were gone. It was like a switch had flipped in her brain.

    As semaglutide has skyrocketed in popularity, patients have been sharing curious effects that go beyond just appetite suppression. They have reported losing interest in a whole range of addictive and compulsive behaviors: drinking, smoking, shopping, biting nails, picking at skin. Not everyone on the drug experiences these positive effects, to be clear, but enough that addiction researchers are paying attention. And the spate of anecdotes might really be onto something. For years now, scientists have been testing whether drugs similar to semaglutide can curb the use of alcohol, cocaine, nicotine, and opioids in lab animals—to promising results.

    Semaglutide and its chemical relatives seem to work, at least in animals, against an unusually broad array of addictive drugs, says Christian Hendershot, a psychiatrist at the University of North Carolina at Chapel Hill School of Medicine. Treatments available today tend to be specific: methadone for opioids, bupropion for smoking. But semaglutide could one day be more widely useful, as this class of drug may alter the brain’s fundamental reward circuitry. The science is still far from settled, though researchers are keen to find out more. At UNC, in fact, Hendershot is now running clinical trials to see whether semaglutide can help people quit drinking alcohol and smoking. This drug that so powerfully suppresses the desire to eat could end up suppressing the desire for a whole lot more.

    The history of semaglutide is one of welcome surprises. Originally developed for diabetes, semaglutide prompts the pancreas to release insulin by mimicking a hormone called GLP-1, or glucagon-like peptide 1. First-generation GLP-1 analogs—exenatide and liraglutide—have been on the market to treat diabetes for more than a decade. And almost immediately, doctors noticed that patients on these drugs also lost weight, an unintended but usually not unwelcome side effect. Semaglutide has been heralded as a potentially even more potent GLP-1 analog.

    Experts now believe GLP-1 analogs affect more than just the pancreas. The exact mechanism in weight loss is still unclear, but the drugs likely work in multiple ways to suppress hunger, including but not limited to slowing food’s passage through the stomach and preventing ups and downs in blood sugar. Most intriguing, it also seems to reach and act directly on the brain.

    GLP-1 analogs appear to actually bind to receptors on neurons in several parts of the brain, says Scott Kanoski, a neurobiologist at the University of Southern California. When Kanoski and his colleagues blocked these receptors in rodents, the first-generation drugs exenatide and liraglutide became less effective at reducing food intake—as if this had eliminated a key mode of action. The impulse to eat is just one kind of impulse, though. That these drugs work on the level of the brain—as well as the gut—suggests that they can suppress the urge for other things too.

    In particular, GLP-1 analogs affect dopamine pathways in the brain, a.k.a. the reward circuitry. This pathway evolved to help us survive; simplistically, food and sex trigger a dopamine hit in the brain. We feel good, and we do it again. In people with addiction, this process in the brain shifts as a consequence or cause of their addiction, or perhaps even both. They have, for example, fewer dopamine receptors in part of the brain’s reward pathway, so the same reward may bring less pleasure.

    In lab animals, addiction researchers have amassed a body of evidence that GLP-1 analogs alter the reward pathway: mice on a version of exenatide get less of a dopamine hit from alcohol; rats on the same GLP-1 drug sought out less cocaine; same for rats and oxycodone. African vervet monkeys predisposed to drinking alcohol drank less on liraglutide and exenatide. Most of the published research has been conducted with these two first-generation GLP-1 drugs, but researchers told me to expect many studies with semaglutide, with positive results, to be published soon.

    In humans, the science is much more scant. A couple of studies of exenatide in people with cocaine-use disorder were too short or small to be conclusive. Another study of the same drug in people with alcohol-use disorder found that their brain’s reward centers no longer lit up as much when shown pictures of alcohol while they were in an fMRI machine. The patients in the study as a whole, however, did not drink less on the drug, though the subset who also had obesity did. Experts say that semaglutide, if it works at all for addiction, might end up more effective in some people than others. “I don’t expect this to work for everybody,” says Anders Fink-Jensen, a psychiatrist at the University of Copenhagen who conducted the alcohol study. (Fink-Jensen has received funding from Novo Nordisk, the maker of Ozempic and Wegovy, for separate research into using GLP-1 analogs to treat weight gain from schizophrenia medication.)  Bigger and longer trials with semaglutide could prove or disprove the drug’s effectiveness in addiction—and identify whom it is best for.

    Semaglutide does not dull all pleasure, people taking the drug for weight loss told me. They could still enjoy a few bites of food or revel in finding the perfect dress; they just no longer went overboard. Anhedonia, or a general diminished ability to experience pleasure, also hasn’t shown up in cohorts of people who take the drug for diabetes, says Elisabet Jerlhag Holm, an addiction researcher at the University of Gothenburg. Instead, those I talked with said their mind simply no longer raced in obsessive loops. “It was a huge relief,” says Kimberly Smith, who used to struggle to eat in moderation. For patients like her, the drug tamed behaviors that had reached a level of unhealthiness.

    The types of behaviors in which patients have reported unexpected changes include both the addictive, such as smoking or drinking, and the compulsive, such as skin picking or nail biting. (Unlike addiction, compulsion concerns behaviors that aren’t meant to be pleasurable.) And although there is a body of animal research into GLP-1 analogues and addiction, there is virtually none on nonfood compulsions. Still, addictions and compulsions are likely governed by overlapping reward pathways in the brain, and semaglutide might have an effect on both. Two months into taking the drug, Mary Maher woke up one day to realize that the skin on her back—which she had picked compulsively for years—had healed. She used to bleed so much from the picking that she avoided wearing white. Maher hadn’t even noticed she had stopped picking what must have been weeks before. “I couldn’t believe it,” she told me. The urge had simply melted away.

    The long-term impacts of semaglutide, especially on the brain, remain unknown. In diabetes and obesity, semaglutide is supposed to be a lifelong medication, and its most dramatic effects are quickly reversed when people go off. “The weight comes back; the suppression of appetite goes away,” says Janice Jin Hwang, an obesity doctor at UNC School of Medicine. The same could be true in at least certain forms of addiction too. Doctors have noted a curious link between addiction and another obesity treatment: Patients who undergo bariatric surgery sometimes experience “addiction transfer,” where their impulsive behaviors move from food to alcohol or drugs. Bariatric surgery works, in part, by increasing natural levels of GLP-1, but whether the same transfer can happen with GLP-1 drugs still needs to be studied in longer trials. Semaglutide is a relatively new drug, approved for diabetes since 2017. Understanding the upshot of taking it for decades is, well, decades into the future.

    Maher told me she hopes to stay on the drug forever. “It’s incredibly validating,” she said, to realize her struggles have been a matter of biology, not willpower. Before getting on semaglutide, she had spent 30 years trying to lose weight by counting calories and exercising. She ran 15 half marathons. She did lose weight, but she could never keep it off. On semaglutide, the obsessions about food that plagued her even when she was skinny are gone. Not only has she stopped picking her skin; she’s also stopped biting her nails. Her mind is quieter now, more peaceful. “This has changed my thought processes in a way that has just improved my life so much,” she said. She would like to keep it that way.

    [ad_2]

    Sarah Zhang

    Source link