Study: Antioxidant flavonol linked to lower risk of Alzheimer's dementia

In continuation of my update on kaempferol, myricetin and  quercetin

 

                                                                 kaempferol

                                                                       

                                                                      myricetin

                                                 

                                                                          Quercetin

        

People who eat or drink more foods with the antioxidant flavonol, which is found in nearly all fruits and vegetables as well as tea, may be less likely to develop Alzheimer's dementia years later, according to a study published in the January 29, 2020, online issue of Neurology, the medical journal of the American Academy of Neurology.

"More research is needed to confirm these results, but these are promising findings," said study author Thomas M. Holland, MD, of Rush University in Chicago. "Eating more fruits and vegetables and drinking more tea could be a fairly inexpensive and easy way for people to help stave off Alzheimer's dementia. With the elderly population increasing worldwide, any decrease in the number of people with this devastating disease, or even delaying it for a few years, could have an enormous benefit on public health."

Flavonols are a type of flavonoid, a group of phytochemicals found in plant pigments known for its beneficial effects on health.

The study involved 921 people with an average age of 81 who did not have Alzheimer's dementia. The people filled out a questionnaire each year on how often they ate certain foods. They were also asked about other factors, such as their level of education, how much time they spent doing physical activities and how much time they spent doing mentally engaging activities such as reading and playing games.

The people were tested yearly to see if they had developed Alzheimer's dementia. They were followed for an average of six years. The researchers used various tests to determine that 220 people developed Alzheimer's dementia during the study.

The people were divided into five groups based on how much flavonol they had in their diet. The average amount of flavonol intake in US adults is about 16 to 20 milligrams per day. In the study, the lowest group had intake of about 5.3 mg per day and the highest group consumed an average of 15.3 mg per day.

The study found that people in the highest group were 48 percent less likely to later develop Alzheimer's dementia than the people in the lowest group after adjusting for genetic predisposition and demographic and lifestyle factors. Of the 186 people in the highest group, 28 people, or 15 percent, developed Alzheimer's dementia, compared to 54 people, or 30 percent, of the 182 people in the lowest group.

The results were the same after researchers adjusted for other factors that could affect the risk of Alzheimer's dementia, such as, diabetes, previous heart attack, stroke and high blood pressure.

The study also broke the flavonols down into four types: isorhamnetin, kaempferol, myricetin and quercetin. The top food contributors for each category were: pears, olive oil, wine and tomato sauce for isorhamnetin; kale, beans, tea, spinach and broccoli for kaempferol; tea, wine, kale, oranges and tomatoes for myricetin; and tomatoes, kale, apples and tea for quercetin.

People who had high intake of isorhamnetin were 38 percent less likely to develop Alzheimer's. Those with high intake of kaempferol were 51 percent less likely to develop dementia. And those with high intake of myricetin were also 38 percent less likely to develop dementia. Quercetin was not tied to a lower risk of Alzheimer's dementia.

Holland noted that the study shows an association between dietary flavonols and Alzheimer's risk but does not prove that flavonols directly cause a reduction in disease risk.

Other limitations of the study are that the food frequency questionnaire, although valid, was self-reported, so people may not accurately remember what they eat, and the majority of participants were white people, so the results may not reflect the general population.

https://en.wikipedia.org/wiki/Myricetin

https://en.wikipedia.org/wiki/Quercetin

https://medicalxpress.com/news/2019-07-high-hemoglobin-linked-dementia.html

Elagolix Cuts Heavy Menstrual Bleeding in Women With Fibroids

In continuation of my update on elagolix

For women with uterine fibroids, elagolix with add-back hormonal therapy is associated with a reduction in heavy menstrual bleeding compared with placebo, according to a study published in the Jan. 23 issue of the New England Journal of Medicine.

William D. Schlaff, M.D., from Thomas Jefferson University in Philadelphia, and colleagues conducted two randomized, placebo-controlled phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to assess the efficacy and safety of elagolix twice daily with hormonal add-back therapy to replace reduced levels of endogenous hormones. Overall, 412 women in UF-1 and 378 in UF-2 were randomly assigned in a 2:1:1 ratio to receive elagolix with add-back therapy, elagolix alone, or placebo. The primary end point was menstrual blood loss <80 mL in the final month of treatment and ≥50 percent reduction in menstrual blood loss from baseline to the final month.

The researchers found that in UF-1 and UF-2, the criteria for the primary end point were met by 68.5 percent of 206 and 76.5 percent of 189 women, respectively, who received elagolix plus add-back therapy, compared with 8.7 percent of 102 and 10 percent of 94 women, respectively, who received placebo. The primary end point was met by 84.1 percent of 104 women and 77 percent of 95 women in UF-1 and UF-2, respectively, who received elagolix alone. With add-back therapy, hypoestrogenic effects of elagolix were attenuated.

"In both trials reported here, the risk of heavy menstrual bleeding among premenopausal women with uterine fibroids was significantly lower among women who received elagolix," the authors write.

Several authors disclosed financial ties to biopharmaceutical companies, including AbbVie, which manufactures elagolix and funded the study.

https://www.nejm.org/doi/full/10.1056/NEJMoa1904351

https://en.wikipedia.org/wiki/Elagolix

Naloxone Prescribing Increasing but Still Very Low

In continuation of my update on Naloxone

Naloxone prescribing has increased but is still very low among patients at risk for opioid overdose, according to a study recently published in the Journal of General Internal Medicine.

Lewei (Allison) Lin, M.D., from the University of Michigan in Ann Arbor, and colleagues compared adults who received opioids and naloxone from January 2014 to June 2017 to those who received opioids without naloxone using a U.S.-wide health insurance claims dataset. A total of 3,963 opioid+naloxone and 19,815 opioid-only patients were matched based on gender, age, month/year of opioid fill, and number of opioid claims.

The researchers found that high opioid daily dosage (50 to <90 morphine milligram equivalents [MME] and ≥90 MME versus <50 MME: adjusted odds ratios, 2.43 and 3.94, respectively), receiving concurrent benzodiazepines (adjusted odds ratio, 1.27), and having a diagnosis of opioid use disorder (adjusted odds ratio, 1.56) were key factors associated with naloxone fills. There was an increase in the percentage of patients receiving naloxone, but by the last six months of the study period, less than 2 percent of patients in any of the key overdose risk factor groups received naloxone.

"Increasing naloxone availability is one of the most promising interventions to reduce opioid overdose," the authors write. "These findings suggest there is substantial further work needed to increase naloxone for patients at risk for opioid overdose."

One author disclosed financial ties to the pharmaceutical industry.

https://link.springer.com/article/10.1007%2Fs11606-019-05423-7

https://en.wikipedia.org/wiki/Naloxone

Suvorexant May Improve Insomnia With Alzheimer Disease

In continuation of my update on Suvorexant

Suvorexant improves total sleep time (TST) in patients with probable Alzheimer disease (AD) dementia and insomnia, according to a study published online Jan. 15 in Alzheimer's & Dementia.

W. Joseph Herring, M.D., Ph.D., from Merck & Co., in Kenilworth, New Jersey, and colleagues randomly assigned patients with both probable AD dementia and insomnia to four weeks of suvorexant 10 mg (136 patients; could be increased to 20 mg based on clinical response) or placebo (141 patients). Overnight polysomnography in a sleep laboratory was used to assess TST.

The researchers found that at week 4, the mean improvement from baseline in TST was 73 minutes for the suvorexant group and 45 minutes for the placebo group. Patients taking suvorexant were twice as likely to show an improvement of ≥60 minutes in TST compared with those taking placebo. In suvorexant-treated patients, somnolence was reported by 4.2 percent of participants versus 1.4 percent of placebo-treated patients.

"Suvorexant did not appear to impair next-day cognitive or psychomotor performance as assessed by objective tests, although these assessments do not constitute a comprehensive assessment of cognition," the authors write.

Several authors disclosed financial ties to pharmaceutical companies, including Merck, which manufactures suvorexant and funded the study.

https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12035

https://en.wikipedia.org/wiki/Suvorexant

Fermented soy products linked to lower risk of death

In continuation of my update on the benefits of soy

Natto with Miso and Mayonnaise

A higher intake of fermented soy products, such as miso and natto, is associated with a lower risk of death, finds a study from Japan published by The BMJ today.

However, the researchers stress that the findings should be interpreted with caution as they may have been affected by unmeasured (confounding) factors.

In Asian countries, especially Japan, several types of soy products are widely consumed, such as natto (soybeans fermented with Bacillus subtilis), miso (soybeans fermented with Aspergillus oryzae), and tofu (soybean curd).

It is, however, still unclear whether different soy products, especially fermented soy products, are associated with specific health effects.

So a team of researchers in Japan set out to investigate the association between several types of soy products and death from any cause ("all cause mortality") and from cancer, total cardiovascular disease (heart disease and cerebrovascular disease), respiratory disease, and injury.

They base their findings on 42,750 men and 50,165 women aged 45-74 years who were taking part in a study based in 11 of Japan's public health centre areas.

Participants filled in detailed questionnaires about their dietary habits, lifestyle, and health status. Deaths were identified from residential registries and death certificates over a follow-up period of nearly 15 years.

The researchers found that a higher intake of fermented soy (natto and miso) was associated with a significantly lower (10%) risk of all cause mortality, but total soy product intake was not associated with all cause mortality.

Men and women who ate natto also had a lower risk of cardiovascular mortality than those who did not eat natto, but there was no association between soy intake and cancer related mortality.

These results persisted even after further adjusting for intake of vegetables, which was higher among those consuming larger portions of natto.

The authors point out that fermented soy products are richer in fibre, potassium and bioactive components than their non-fermented counterparts, which may help to explain their associations.

However, this is an observational study, so can't establish cause, and the researchers cannot rule out the possibility that some of the observed risk may be due to other unmeasured factors.

They conclude: "In this large prospective study conducted in Japan with a high rate of soy consumption, no significant association was found between intake of total soy products and all cause mortality. In contrast, a higher intake of fermented soy products (natto and miso) was associated with a lower risk of mortality."

Increasing evidence has suggested that fermented soy products are associated with health benefits, write researchers in a linked editorial. Whether people eat those products depends on their food culture, they say, but some countries already include soy and fermented soy products in their dietary guidelines.

Further studies are still required, however, "to refine our understanding of the health effects of fermented soy, and perhaps to inform the development of healthier and more palatable products," they conclude. "These efforts should be collaborative, including not only researchers but also policy makers and the food industry."

https://phys.org/news/2018-09-video-natto-stinky-slimy-soybean.html

Researchers uncover two-drug combo that halts the growth of cancer cells

                       Everolimus

Neratinib

In continuation of my update on Neratinib  and Everolimus

UT Southwestern Simmons Cancer Center researchers have discovered a two-drug combo that halts the growth of cancer cells that carry HER2 mutations.

The findings, published today in the journal Cancer Cell, were prompted by the observation that, after an initial response, patients with cancers harboring HER2 mutations eventually develop resistance to a promising new cancer drug currently in clinical trials.

The scientists found that another drug, already on the market, counters that resistance and blocks the cancer, thereby providing the basis for a novel drug combination against cancers with mutations in the HER2 gene.

Dhivya Sudhan, Ph.D., a postdoctoral research fellow in the Harold C. Simmons Comprehensive Cancer Center, and collaborators evaluated data from a molecularly guided trial where patients with tumors with HER2 mutations were treated with the HER2 inhibitor neratinib. In this study, patients' cancers were sequenced as the disease progressed during treatment. Based on this analysis, Sudhan discovered in the laboratory that an effective way to offset eventual resistance to neratinib is with everolimus, a TORC1 inhibitor commonly used to treat other types of breast cancer.

"This finding may give clinicians an effective response to neratinib resistance. That could make a real difference for patients with breast, ovarian, lung, and other cancers harboring HER2 mutations," says Carlos L. Arteaga, M.D., Director of the Simmons Cancer Center at UT Southwestern and corresponding author of the study.

HER2 mutations have long been identified as a key driver in breast and other cancers. The authors of this study zeroed in on a signaling network driven by TORC1, which they showed is the pathway through which HER2-mutant cancers become neratinib-resistant.

"We consistently noted activation of TORC1 signaling as a mechanism of resistance to neratinib across different types of HER2-mutant cancers. Different cancer types used different strategies to escape neratinib, but they all converged on TORC1 signaling," Sudhan says.

In addition to studying tumor sequencing data from HER2-mutant cancer patients across the country who are in clinical trials for neratinib, Sudhan also studied neratinib-resistant cells and tumors that continue to live and grow in the laboratory.

The sequencing of the patients' cancer before and during the clinical trial showed that some patients already had a mutation that could activate the TORC1 pathway. Others would develop it eventually, but they could benefit from everolimus which is currently used as a TORC1 inhibitor to address the other roles TORC1 plays in cancer. Everolimus would allow the patient to continue benefiting from neratinib's inhibition of HER2.

Sudhan says the combination of neratinib and everolimus worked in cell lines, organoids established from patient-derived tumors, and in mice harboring HER2 mutant tumors. The next step will be testing this two-drug combo in humans.

https://en.wikipedia.org/wiki/Neratinib

https://en.wikipedia.org/wiki/Everolimus

https://www.sciencedirect.com/science/article/abs/pii/S1535610819305835?via%3Dihub

Taking aim at gastric cancer: New approach to selective chemotherapy

A novel drug, named "FerriIridium," can simultaneously help diagnose and treat gastric cancer. The initially weakly active precursor (prodrug), based on an iridium-containing compound, is selectively activated only after reaching the interior of a tumor cell. This is possible because of the higher amount of iron present there, report scientists in the journal Angewandte Chemie. Selective activation reduces undesired side effects.

Cells transport substances from their exterior to their interior by folding in small regions of their membrane and then binding them off (endocytosis). This is how FerriIridium enters target cells. The resulting vesicles then fuse with lysosomes. These cell organelles have an acidic environment that contains trivalent iron ions, Fe(III), and enzymes, with which they dismantle cell components that are no longer needed. In gastric cancer cells, the Fe(III) concentration within the lysosomes is significantly elevated.

Scientists working with Yu Chen and Hui Chao at Sun Yat-Sen University, Guangzhou, and Hunan University of Science and Technology, Xiangtan (China) made use of this feature. They equipped FerriIridium with a special functional group (the m-iminocatechol group) that selectively binds to Fe(III). When bound, the functional group is oxidized while the iron ions are reduced to Fe(II). Under the acidic conditions within the lysosomes, the FerriIridium is then split into two components: an iridium complex and a benzoquinone derivative.

This reaction mechanism has a threefold effect. First, Fe(II) ions can catalyze a reaction that produces highly reactive hydroxyl radicals. Second, benzoquinones are highly oxidizing. With certain cellular substances, such as NADPH, they form hydroxyquinones, which react with oxygen to produce radical oxygen species, as well as hydrogen peroxide, which in turn can react with Fe(II) to produce hydroxyl radicals. Benzoquinone compounds can also disrupt cellular respiration. The radicals destroy the lysosomes, releasing their contents. Third, the splitting of FerriIridium drastically increases both the phosphorescence and the toxicity of the iridium complex. The phosphorescence can be used to diagnose the tumor. Most importantly, however, the toxic iridium complex is absorbed by mitochondria, the "cellular power plants." It destroys them from the inside out by collapsing their membrane potential. Together, these effects lead to the death of the gastric cancer cells and shrinking of the tumors, as demonstrated by experiments on cell lines and mice.

https://www.chemistryviews.org/details/ezine/11214563/Taking_Aim_at_Gastric_Cancer.html

Walnuts may slow cognitive decline in at-risk elderly: Two-year study examined walnut consumption among study groups in California and Spain

In continuation of my update on Walnuts

Eating walnuts may help slow cognitive decline in at-risk groups of the elderly population, according to a study conducted by researchers in California and Spain.

The Walnuts and Healthy Aging Study, published this month in The American Journal of Clinical Nutrition, found that walnut consumption by healthy, elderly adults had little effect on cognitive function over two years, but it had a greater effect on elderly adults who had smoked more and had a lower baseline neuropsychological test scores.

The study examined nearly 640 free-living elders in Loma Linda, California, USA, and in Barcelona, Catalonia, Spain. For two years, the test group included walnuts in their daily diet, and the control group abstained from walnuts.

Walnuts contain omega-3 fatty acids and polyphenols, which have previously been found to counteract oxidative stress and inflammation, both of which are drivers of cognitive decline.

Joan Sabaté, MD, DrPH, professor of nutrition and epidemiology at Loma Linda University School of Public Health and the study's principal investigator, said this was the largest and most well-controlled trial ever conducted on the effects of nuts on cognition.

"While this was a minor result, it could lead to better outcomes when conducted over longer periods of time," Sabaté said. "Further investigation is definitely warranted based on our findings, especially for disadvantaged populations, who may have the most to gain from incorporating walnuts and other nuts into their diet."

Sabaté and his research team at Loma Linda University were the first to discover the cholesterol-lowering effect of nut consumption -- specifically walnuts -- with lowering blood cholesterol. Findings were first published in the New England Journal of Medicine in 1993.

Subsequently, findings from Loma Linda University researchers have linked nut consumption to lower risk of cardiovascular diseases.

The Walnuts and Healthy Aging Study was funded by a grant from the California Walnut Commission, which had no input in the study design, data collection, analyses, or writing and submission of the manuscript.

https://news.llu.edu/research/walnuts-may-slow-cognitive-decline-risk-elderly

FDA Acceptance of ALKS 3831 New Drug Application for Treatment of Schizophrenia and Bipolar Disorder

 Alkermes plc (Nasdaq: ALKS) announced that the U.S. Food and Drug Administration (FDA) has accepted for review the company's New Drug Application (NDA) seeking approval of ALKS 3831 (olanzapine/samidorphan) for the treatment of schizophrenia and for the treatment of bipolar I disorder. ALKS 3831 is an investigational, novel, once-daily, oral atypical antipsychotic drug candidate designed to provide the efficacy of olanzapine while mitigating olanzapine-associated weight gain. The NDA has been assigned a Prescription Drug User Fee Act (PDUFA) target action date of Nov. 15, 2020. [(Olanzapine/samidorphan - developmental code name ALKS-3831) is a combination of the atypical antipsychotic olanzapine and the opioid modulator samidorphan

                             

                                                                                             Samidorphan

olanzapine

"The acceptance of the NDA for ALKS 3831 marks an important milestone toward our goal of offering a new treatment option to people living with schizophrenia or bipolar I disorder. The ALKS 3831 development program builds on Alkermes' commitment to developing new therapeutic options that seek to address unmet needs of patients in large therapeutic areas," said Craig Hopkinson, M.D., Chief Medical Officer at Alkermes. "We believe ALKS 3831 has the potential to be a meaningful new offering for patients with these serious and complex mental health disorders, and we look forward to engaging with the FDA throughout the NDA review process."

The ALKS 3831 NDA includes data from the ENLIGHTEN clinical development program in patients with schizophrenia, as well as pharmacokinetic (PK) bridging data comparing ALKS 3831 and ZYPREXA^® (olanzapine), to support an indication for the treatment of schizophrenia, and an indication for the treatment of manic or mixed episodes associated with bipolar I disorder as a monotherapy or adjunct to lithium or valproate and for maintenance treatment of bipolar I disorder. Alkermes is seeking approval of fixed dosage strengths of ALKS 3831 composed of 10 mg of samidorphan co-formulated with 5 mg, 10 mg, 15 mg or 20 mg of olanzapine.

About the ENLIGHTEN Clinical Development Program

The ENLIGHTEN clinical development program for ALKS 3831 includes two key studies in patients with schizophrenia: the ENLIGHTEN-1 study, which evaluated the antipsychotic efficacy of ALKS 3831 compared to placebo over four weeks, and the ENLIGHTEN-2 study, which assessed weight gain with ALKS 3831 compared to olanzapine over six months. The program also includes supportive studies to evaluate the pharmacokinetic and metabolic profile and long-term safety of ALKS 3831, and pharmacokinetic bridging studies comparing ALKS 3831 and ZYPREXA.

About ALKS 3831

ALKS 3831 is an investigational, novel, once-daily, oral atypical antipsychotic drug candidate for the treatment of schizophrenia and bipolar I disorder. ALKS 3831 is composed of samidorphan, a novel, new molecular entity, co-formulated with the established antipsychotic agent, olanzapine, in a single bilayer tablet.

About Schizophrenia 

Schizophrenia is a serious brain disorder marked by positive symptoms (hallucinations and delusions, disorganized speech and thoughts, and agitated or repeated movements) and negative symptoms (depression, blunted emotions and social withdrawal).An estimated 2.4 million American adults have schizophrenia, with men and women affected equally.

About Bipolar I Disorder

Bipolar disorder is a brain disorder that causes shifts in a person's mood, energy and ability to function. Patients with this brain disorder may experience debilitating mood shifts from extreme highs (mania) to extreme lows (depression). Bipolar I disorder is characterized by the occurrence of at least one manic episode, with or without the occurrence of a major depressive episode, and affects approximately one percent of the adult population in the United States in any given year.

About Alkermes plc

Alkermes plc is a fully integrated, global biopharmaceutical company developing innovative medicines for the treatment of central nervous system (CNS) diseases and oncology. The company has a diversified commercial product portfolio and a clinical pipeline of product candidates for diseases that include schizophrenia, depression, addiction, multiple sclerosis, and cancer. Headquartered in Dublin, Ireland, Alkermes plc has an R&D center in Waltham, Massachusetts; a research and manufacturing facility in Athlone, Ireland; and a manufacturing facility in Wilmington, Ohio. For more information, please visit Alkermes' website at www.alkermes.com.

https://en.wikipedia.org/wiki/Olanzapine

https://en.wikipedia.org/wiki/Samidorphan

Could a Common Diuretic Med Help Ease Autism Symptoms?

A prescription drug that's long been used to treat the buildup of fluid in the body might do double duty as a means of easing autism symptoms in young children, new research shows.

If replicated in future trials, the drug treatment might be a breakthrough, since current treatments for autism in preschool kids are mainly behavioral -- therapies such as using play and activities with parents to improve a child's language, social and thinking skills.

The drug bumetanide is currently used to help reduce fluid-linked swelling that comes with heart failure or kidney disease.

But bumetanide may improve autism symptoms by affecting two chemical "messengers" that help nerve cells in the brain communicate. The drug appears to lower the ratio of one key brain chemical called GABA, to another chemical called glutamate, explained a team from the University of Cambridge and several institutions in Taiwan and China.

It's this mechanism that appears to help ease autism symptoms.

"This is the first demonstration that bumetanide improves brain function and reduces symptoms by reducing the amount of the brain chemical GABA," said researcher Ching-Po Lin, of National Yang-Ming University in Taipei, Taiwan.

Speaking in a Cambridge news release, he said, "Understanding this mechanism is a major step towards developing new and more effective drug treatments."

Study co-author Barbara Sahakian, from Cambridge's department of psychiatry, agreed.

"This study is important and exciting because it means that there is a drug that can improve social learning and reduce [autism] symptoms during the time when the brains of these children are still developing," she said in the release.

"We know that GABA and glutamate are key chemicals in the brain for plasticity and learning and so these children should have an opportunity for a better quality of life and well-being," Sahakian said.

According to the researchers, prior studies in rats and small clinical trials involving children had suggested that bumetanide might help reduce symptoms of autism.

The new study was still relatively small -- just 83 children with autism, ranging between 3 to 6 years of age. The children were divided: One group of 42 received 0.5 milligrams of bumetanide twice a day for three months, while a "control" group of 41 children received no treatment.

Along with reducing autism symptoms, bumetanide appeared to cause no significant side effects, according to the study published Jan. 26 in Translational Psychiatry.

Any medicine that might alleviate autism symptoms would be very welcome, because behavioral treatments are not always accessible, particularly in developing countries, the research team noted.

"I have many children with autism spectrum disorder under my care, but as psychological treatment resources are not available in many places, we are unable to offer them treatment. An effective and safe treatment will be very good news for them," study clinical leader Dr. Fei Li, of Jiao Tong University School of Medicine in Shanghai, said in the release.

Dr. Andrew Adesman directs developmental and behavioral pediatrics at Cohen Children's Medical Center of New York in New Hyde Park. He wasn't involved in the new study,  but was cautiously optimistic about the results.

Future trials will reveal how useful bumetanide might be against autism.

"Several methodologically rigorous, double-blind, placebo-controlled studies are now underway," Adesman noted, "and we should know much more in a year or two as to whether bumetanide is indeed safe and effective."

The current trial did have one key shortcoming, he said.

"Because this study lacked a placebo control group, it is hard to know if all of the clinical improvements reported were due to the bumetanide treatment itself or to placebo effects," Adesman said. But he said certain brain scan evidence presented in the study does suggest a real and beneficial effect.

Adesman added that parents should probably not demand the drug for their kids just yet, however.

"I think families should wait until we know a little more about its potential benefits and side effects," he said. "We need a methodologically rigorous, well-designed clinical trial to better assess the clinical benefits of bumetanide."

https://en.wikipedia.org/wiki/Bumetanide