A commonly available oral diuretic pill, bumetanide, has been approved by the U.S. Food and Drug Administration and shows potential for Alzheimer's disease treatment. 

In an analysis of clinical trials conducted, those who took bumetanide reported having a lower prevalence of Alzheimer’s disease compared to those who did not take the drug. Researchers analyzed data databases of brain tissue samples and FDA-approved drugs, performed mouse and human cell experiments, and explored human population studies to identify bumetanide as a leading drug candidate that may potentially be repurposed to treat Alzheimer's. The findings were published in 

"Though further tests and clinical trials are needed, this research underscores the value of big data-driven tactics combined with more traditional scientific approaches to identify existing FDA-approved drugs as candidates for drug repurposing to treat Alzheimer's disease," said NIA Director Richard J. Hodes, M.D.

Researchers retrieved data from 213 brain tissue samples and researchers identified Alzheimer's gene expression signatures and studied the levels to which the genes were turned on or off, specific to APOE4 carriers. One of the main genetic risk factors for Alzheimer's is a form of the apolipoprotein E gene, APOE4.

Further, scientists compared the APOE4-specific Alzheimer's signatures against over 1,300 established FDA-approved drugs. Five drugs became known with a gene expression signature thought to counteract the disease. The strongest candidate of those studied was bumetanide. Bumetanide is used to treat fluid retention caused by heart, kidney, and liver disease.

Bumetanide was tested in both mouse models of Alzheimer's and induced pluripotent stem cell-derived human neurons. It was found that treating mice which expressed the human APOE4 gene lessened learning and memory deficits.

The neutralizing effects were established in the human cell-based models. Therefore, people already taking bumetanide were expected to have lower rates of Alzheimer's. Health record data sets from over 5 million people were studied in two groups: those over age 65 who took bumetanide and a control group who did not take the drug.

The results showed that those who had the genetic risk and took bumetanide had a 35 percent to 75 percent lower prevalence of Alzheimer's disease compared to those not taking the drug.

"We know that Alzheimer's disease will likely require specific types of treatments, perhaps multiple therapies, including some that may target an individual's unique genetic and disease characteristics -- much like cancer treatments that are available today," said Jean Yuan, M.D., Ph.D., Translational Bioinformatics and Drug Development program director in the NIA Division of Neuroscience.

Precision Medicine Data Dive shows diuretic pill may be viable to test as Alzheimer’s treatment

. ScienceDaily. Accessed October 12, 2021.

Articles

A commonly available, FDA-approved oral diuretic pill may be a potential candidate for Alzheimer's disease treatment, according to new research.

Common Oral Diuretic Pill as Alzheimer’s Treatment, Study Shows

The upcoming webinar event “Get to Know Good Neighbor Pharmacy & the Four Core Value Centers” will help independent pharmacies optimize their business and secure their position as a vital source of care in the community.

The event, which will be held on Tuesday, October 19, will provide actionable insights to help independent pharmacists strengthen their defining attributes by enhancing their current practices. Brought to you by AmerisourceBergen and 

 (GNP), the webinar will equip independent pharmacies with the information they need to improve their performance, develop deeper patient relationships, and secure their legacy within their communities.

Katie Collins, Director of GNP at AmerisourceBergen, will introduce viewers to the GNP network and discuss the 4 core value centers pharmacies should focus on:

 Leave a positive impression on every person who walks through your door by using proven tools and expert guidance to deliver the kind of experience your patients are craving.

: Attract more patients and build loyalty by executing proven marketing strategies that showcase your unique brand and extend your reach within your community.

 Maximize profit margin and minimize profit leakage with solutions that combine analytics, technology, and professional services to ensure you get the reimbursement you deserve.

 Perfect how your pharmacy operates with the help of a dedicated business coach who will combine deep industry knowledge with data-driven insight to improve your profitability.

The program aims to provide support where it’s needed most and help pharmacies simplify business operations, amplify brand and identity, and protect their independence.

Don't miss our upcoming webinar with Good Neighbor Pharmacy, focused on helping independent pharmacies optimize their business. 

Get to Know Good Neighbor Pharmacy and the 4 Core Value Centers

Women Pharmacist Day will take place on October 12. Join Drug Topics® in celebrating all those women pharmacists have accomplished and the many contributions made every day. Quality care is at the forefront of pharmacy and these pharmacists deserve to be celebrated for all of their hard work and quality care throughout the past year.

October is additionally National Pharmacist Month and was selected for this special day to extend this celebration. The first woman pharmacist in the nation was Elizabeth Gooking Greenleaf. She was both a mother and pioneer for women in pharmacy and October 12 honors her. 

Currently, women make up 75 percent of the workforce in this field. Sixty years ago, this number was 8 percent. Women have made amazing strides in earning PharmDs and becoming pharmacists, with over half of all PharmDs graduates being women.

Women Pharmacist Day is about celebrating these women for being the healthcare providers that are trusted in their communities for other women. Women, for example, make up approximately 80 percent of decisions regarding purchasing for their families, according to the statistics.

 to join in the conversation highlighting these women. Comment your favorite woman pharmacist on October 12 and thank the female pharmacists in your life. Use the hashtag #WomenPharmacistDay and head to our 

1. Women Pharmacist Day. https://womenpharmacistday.com/. Accessed October 7, 2021.

2. National Pharmacy Week. ASHP. https://pact.ashp.org/Pharmacy-Practice/Resource-Centers/Public-Relations/National-Pharmacy-Week. Accessed October 7, 2021.

3. Apha Foundation. APhA Foundation. https://www.aphafoundation.org/. Accessed October 8, 2021.

The fourth annual Women Pharmacist Day will take place on October 12 and honor the many strides made by women in pharmacy. Head to the Drug Topics® social media pages to celebrate.


Celebrate National Women Pharmacist Day 2021

The fourth annual Women Pharmacist Day will take place on Tuesday, October 12 and honor the notable strides women have made in pharmacy.

https://www.drugtopics.com/view/celebrate-national-women-pharmacist-day-october-12

Pack4U: Medication Delivery and Patient Monitoring Part 1


In part 1 of this 2-part series, Shane Bishop, Pack4U founder, discusses how Pack4U has created a pharmacy network making it easier for pharmacies to deliver medications and provide personalized care within their community.


https://www.drugtopics.com/view/part-1-pack4u-medication-delivery-and-patient-monitoring?seriesVid=1

Women's Health Series: Biosimilars Interview Part 1

In part 1 of this series, Dr. Mallampalli sits down with Drug Topics® to discuss biosimilars as a treatment option for chronic health conditions and their impact on women’s health.

https://www.drugtopics.com/view/women-s-health-series-biosimilars-interview?seriesVid=1

Women’s Health Series: Menopausal Hormone Therapy Not Linked to Dementia

A study published in The BMJ reveals that menopausal hormone therapy is not linked to an increased risk of developing dementia in women.

https://www.drugtopics.com/view/women-s-health-series-menopausal-hormone-therapy-not-linked-to-dementia

Here’s a roundup of the latest news coverage from Drug Topics®.

News Roundup: Women Pharmacist Day, Women's Health Series

Expert Interview: Shane Bishop Part 1

In part 1 of this 2-part series, Shane Bishop, Pack4U founder, discusses how Pack4U has created a pharmacy network, making it easier for pharmacies to deliver medications and provide personalized care within their communities.

 I'd love to get right into our topic. Could you start by telling me a little bit about your background?

Yeah, sure. We also I am, you know, pharmacist by profession. In the early days, I was I was actually the first pharmacist to adopt multi dose trip packaging, into pharmacies that are owned and operated here in Western Canada.

I quickly ended up tracking all the inefficiencies and miscommunications based around that new packaging format. As we deployed it to long term care facilities and ended up creating an electronic electronic medication administration record that actually links multi dose trip packaging, to the bedside and scanning barcodes to real time information flow between pharmacy and long term care facility in nursing.

We really look to eliminate, you know, medication related errors at the bedside. So that was a, my, my first involvement from pharmacists into technology.

 Wow, that's so cool. Could you tell me a little bit about pack for you itself and the company's mission?

Yeah, pack for you itself is absolutely focused on its core, which is to be the absolute best at driving true medication adherence for patients, whether they're in long term care facilities, you know, patients at home with with multiple chronic conditions.

You know, that's our goal. And I you know, we I think we have the, the only true fully integrated end to end solution with technology and services that allow us to drive what I term true medication adherence.

Wow, that's awesome. Who is your focus, and where can providers and patients find your services?

I mean, our focus is different in both Canada and the US. In Canada, we've established a network of pharmacies across all the provinces that I would call super innovative pharmacies and pharmacists that want to do better for the patients in their community.

So, we leverage our network of pharmacies across Canada, and actually provide help with marketing via direct to consumer of campaigns, you know, Facebook, etc, with some of our solutions, and drive these higher risks, you know, chronic patients to our pharmacy network, which has been has been amazing for the patients and the pharmacies, as well.

In Canada, we actually spend a lot of time working with government to collect data, do studies within those structures, and really try to define and look at total cost of care reductions for those entities. So that's kind of what we're doing in Canada. So kind of a two pronged approach. In the US, we really are focused on health plans, the payers looking to, you know, ultimately increase heeta scores and measures, drive up star ratings. 

Can you tell me a little bit about your transitional care management?

 Yeah, when it comes to, you know, transition of care, I guess, ultimately, with our solution, we really are trying to focus on patients remaining in the home, which I think is the goal for a number of different you know, healthcare organizations, companies out there, you know, remote patient monitoring chronic care management, you know, from a distance with our clinical pharmacists team is all about keeping keeping patients at home and keeping them out.

Moving into the more acute settings. When we look at, you know, patients being discharged from hospital, it makes a lot of sense for a number of the conditions such as congestive heart failure to definitely keep a patient adherent to their medications and have some form of connected care co hub in the home. 

So, look at real time, not only medication adherence to make sure the patients are taking their medications that they've been discharged with, but also looking at real time, blood pressure and weight, and have a team of proactive clinic clinicians around that data to really take care of the patients and ensure that they don't end up back in the acute care setting.

Expert Interviews

In part 1 of this 2-part interview, Shane Bishop, Pack4U founder discusses the benefits of medication delivery and remote services for pharmacists.

Pack4U: Medication Delivery and Patient Monitoring Part 1

This article was originally published on 

Representatives from NFID and the Centers for Disease Control and Prevention (CDC) held a press conference yesterday to discuss the findings and encourage everyone 6 months or older to receive the annual flu vaccine.

“Pregnant women are at risk for severe influenza infection, which means a greater risk for hospitalization, ICU admission, and death,” said Laura E. Riley, MD, obstetrician and gynecologist-in-chief at New York Presbyterian/Weill Cornell Medical Center and chair of the Department of Obstetrics and Gynecology at Weill Cornell Medical Center, New York City, New York.

“Nearly half of pregnant women and their infants remain unprotected against the flu,” Riley said.

 Survey results showed a coverage rate of 55% among pregnant women, similar to the prior season.

“An important effect of the vaccine when given during pregnancy is that maternal antibodies to influenza cross the placenta and provide protection for the neonate in the first few months of life, when the baby is at high risk for severe disease and is not eligible for its vaccination,” Riley told 

NFID’s annual survey collected information on attitudes and behaviors around flu, pneumococcal disease, and COVID-19 for the 2020 to 2021 flu season.

 Results showed that, in adults 65 and older or those at higher risk for pneumococcal disease, 51% are not familiar with pneumococcal disease. More startling, is that only about one-third (32%) of respondents reported being advised to get vaccinated against pneumococcal disease.

Racial and ethnic disparities in flu vaccine uptake were evident, with Hispanic adults (52%) and Black adults (45%) more likely to be worried about contracting both COVID-19 and the flu at the same time compared to White adults (27%).

“Given the risk of the disease, the clear benefit of vaccination and the ample safety data makes it a no-brainer in terms of what needs to happen,” Riley said.

CDC. 2020-21 Flu Season Summary FAQ. . Accessed October 7, 2021. 

https://www.cdc.gov/flu/season/faq-flu-season-2020-2021.htm#anchor_1627000392551

National Foundation for Infectious Diseases. US Health Officials Urge Vaccination Amid Concerns About Influenza Resurgence During Ongoing Pandemic. Prnewswire.com. Published October 7, 2021. Accessed October 8, 2021. 

https://www.prnewswire.com/news-releases/us-health-officials-urge-vaccination-amid-concerns-about-influenza-resurgence-during-ongoing-pandemic-301394791.html

According to new survey data from the National Foundation for Infectious Diseases, nearly 1 in 4 people at high risk for flu-related complications, such as pregnant women, did not plan to get vaccinated.

Flu Survey Results Reveal Vulnerability of Pregnant Women

Study on Pregnant Women Points to Importance of Timely Flu Vaccination

Researchers examined the effects of severe acute respiratory infections on pregnancy and reported some concerning findings.

https://www.drugtopics.com/view/study-on-pregnant-women-points-to-importance-of-timely-flu-vaccination

UAMS Team Wins 2021 Good Neighbor Pharmacy NCPA Pruitt-Schutte Student Business Plan Competition

Winners were announced during the NCPA Annual 2021 Convention.

https://www.drugtopics.com/view/uams-team-wins-2021-good-neighbor-pharmacy-ncpa-pruitt-schutte-student-business-plan-competition

Validcare Researchers Discuss Results of CBD Liver Toxicity Study

Co-principal investigators Jeff Lombardo and Keith Aqua discuss the unique patient profiles of the study, future cohorts, and FDA's response to the findings.

https://www.drugtopics.com/view/validcare-researchers-discuss-results-of-cbd-liver-toxicity-study

https://www.drugtopics.com/view/common-oral-diuretic-pill-as-possible-alzheimer-s-treatment-study-shows

Don't miss our upcoming webinar with Good Neighbor Pharmacy, focused on helping independent pharmacies optimize their business.

https://www.drugtopics.com/view/get-to-know-good-neighbor-pharmacy-and-the-4-core-value-centers

The fourth annual Women Pharmacist Day will take place on October 12 and honor the many strides made by women in pharmacy. Head to the Drug Topics® social media pages to celebrate.

News Roundup: NCPA Student Business Finalist, CBD Liver Toxicity Study

A recent study found that poor timing between season influenza transmission and national annual vaccination campaigns led to an increase in premature births, lower birthweight and an increase in babies delivered by cesarean section.

 The study underscores the importance for timely influenza vaccinations amid the continuing COVID-19 pandemic.

Globally, respiratory infections are a leading cause of disease and death, but its adverse effects on pregnant women remain understudied and are especially pronounced in low- and middle-income countries, according to researchers.

Study authors cited findings from several previous studies, which found that influenza during pregnancy is associated with increased hospitalization, late pregnancy loss and low birthweight, among other effects.

Investigators from the University of Virginia School of Medicine and the Federal University of Ceará in Brazil collaborated to analyze the effect of SARI on pregnancy by identifying peak influenza activity among various regions in Brazil and reviewing SARI, influenza, and influenza vaccinations in the state between 2013 and 2018. In the semiarid state of Ceará, peak seasonal influenza activity normally begins in mid-May, but influenza circulation may start as soon as mid-March, according to the study. Importantly, despite regional differences among influenza seasons – for example, Fortaleza, the state capital, has a seasonal peak 2-3 months earlier than Ceará – Brazil utilizes the same national vaccination schedule.

“Because vaccine-acquired immunity against influenza usually develops 2 weeks after immunization, we hypothesized that pregnant women and their fetuses in the semiarid region might not be adequately protected against influenza,” study authors wrote.

Between 2013 and 2018, of 3297 recorded SARI cases, 145 (4.4%) occurred in pregnant women. The research team reported that 30 to 40 weeks after the peak of the influenza season, birthweights decreased by 40 g and prematurity rates increased from 10.7% to 15.5%. The study identified 61 children born to mothers with SARI during pregnancy, who weighed 10% less at birth and were more likely to be premature than 122 newborn controls. In addition, mothers who had SARI during pregnancy had significantly less formal education than mothers who did not have SARI.

“Our study aligns with earlier reports showing the importance of prevention and adjustment of influenza vaccine campaign schedules to avoid complications of influenza,” authors wrote. “Further work is urgently needed to model and study the optimal timing, potential impact, logistics, economics, and implementation of such a diversified national influenza strategy,” they concluded.

Filho JQ, Junior FS, Lima TBR, et al. Perinatal outcomes of asynchronous influenza vaccination, Ceará, Brazil, 2013-2018. Centers for Disease Control and Prevention (CDC). September 2021. Accessed October 13, 2021. 

https://wwwnc.cdc.gov/eid/article/27/9/20-3791_article

Troubling birth findings show importance of timely flu vaccination. News Release. ScienceDaily; October 13, 2021. Accessed October 13, 2021. 

https://www.sciencedaily.com/releases/2021/10/211013094124.htm

Researchers examined the effects of severe acute respiratory infections on pregnancy and reported some concerning findings. 

Study on Pregnant Women Points to Importance of Timely Flu Vaccination 

Lauren Biscaldi is the Managing Editor of Drug Topics. 

A student pharmacist team from the University of Arkansas for Medical Sciences College of Pharmacy has been selected as the winner of the 18th Annual Good Neighbor Pharmacy (GNP) National Community Pharmacists Association (NCPA) Pruitt-Schutte Student Business Plan Competition.

Runners-up included teams from the University of Texas at Austin College of Pharmacy and the Medical University of South Carolina. All winners were announced as a part of the NCPA 2021 Annual Convention, held October 9 through 12 in Charlotte, North Carolina. These finalists presented their business plans live on October 9, with winners announced the following day.

In an NCPA press release, Brian Caswell, owner of Wolkar Drug in Baxter Springs, Kansas, and NCPA President, applauded each participating team.

“After a highly competitive live competition, one team stood out above the rest. With these well-thought-out business plans, the future of independent pharmacy is in good hands,” he said.

This year’s slate of teams included student pharmacists from 23 schools and colleges of pharmacy across the US who participated in the first-of-its-kind business plan competition. The goal of the competition—named for Neil Pruitt, Sr. and H. Joseph Schutte—is to motivate student pharmacists to “create a business model for buying an existing independent community pharmacy or developing a new one,” according to the press release.

The winning team included team captain Jason Lam and team members Michael Kramer, Bobby Le, and Rachel Murray; Seth Heldenbrand, PharmD, served as team adviser and Cindy D. Stowe, PharmD, as Dean. A prize of $3000 was awarded, with an additional $3000 contribution made to the school in Dean Stowe’s name to promote independent community pharmacy at the UAMS College of Pharmacy.

This article was written in partnership with AmerisourceBergen and Good Neighbor Pharmacy

UAMS College of Pharmacy Wins 2021 Good Neighbor Pharmacy NCPA Pruitt-Schutte Student Business Plan Competition. News Release. National Community Pharmacists Association (NCPA). October 10, 2021. Accessed October 12, 2021. 

https://ncpa.org/newsroom/news-releases/2021/10/10/uams-college-pharmacy-wins-2021-good-neighbor-pharmacy-ncpa

 I’m Jeff Lombardo, I'm an oncology pharmacist by training, a research assistant professor at the University of Buffalo and I'm a co-principal investigator on this liver toxicity study.

 My name is Keith Aqua. I'm also co-principal investigator on the study. I am a practicing physician who has been in the cannabidiol (CBD) and cannabis space for about 2-3 years, and a clinical trial investigator for over 25 years.

 and cannabinoids have been available for many years, and in the United States and around the world. There is a lack of regulation in the United States, except for a very exclusive company, which is some very specific indications for pediatric seizure disorders. There's not a lot of safety and efficacy data. The FDA, as well as other governing regulatory bodies, are looking to researchers and to companies to find the safety and efficacy data, so they can make claims. There are a lot of consumers and customers and patients that are taking CBD on their own, assuming that it's safe and not really having an understanding of the drug interactions, or possibly how it can affect other organ systems.

So Valid Care asked Jeff and I and some other investigators to look at a population of patients, particularly liver function tests and some other secondary endpoints that we had, to try to add to the data that exists for safety. And potentially use this data to launch other companies to do research on efficacy.

 I think, as Dr. Aqua said, with increased utilization and uptake, and basically more people using it, safety is always the number 1 concern, and then efficacy comes second. But this was a safety study looking at liver toxicity and focusing on potential drug interactions that can occur. And some of this was based on some of the previous literature, some of the reports with elevated liver function tests with some other previously reported products.

 And briefly, these products have been around for a long time. But with the passing of the Farm Bill in December of 2018, it legalized the production of hemp. And with that it opened up the gates, as Jeff said, to CBD products being produced. And with that, that's where some very good companies, which really focused on research and development and making sure that they were producing product with the utmost detail, they were some good players in the market. And then of course, the market got flooded by individuals just producing products that maybe was not at the highest quality. And I think that's what has scared a lot of individuals, and rightfully so.

 a lot of the products, they're marketed as dietary supplements. You can find them in supermarkets, you can find them in convenience stores, you can get direct to consumers from some of the companies. It’s a different pathway than FDA approved medications and really doesn’t have standardized dosing of how much you should take for certain indications. So, there's those questions.

When we've tested some of these products in the lab, there's really been a question about potency; of what is in the bottle isn't on the label. One important thing about this study is that we received a Certificate of Analysis (COA) for all 12 companies that participated in these studies. And these are reputable companies, so what was on the label was verified and was on the COA. And really, I would say they are some of the good players in the space.

 Just to add to what Jeff said, there are some studies out there that show that anywhere between 60 and 80% of CBD products on the market and on the shelves right now are mislabeled. So, either there's no CBD in that product or there's too much CBD in that product. So, again, re-emphasizing what Jeff said, the individual companies that work on this clinical trial really are above the standard.

 This study, the companies that participated, chose a product that they wanted to be involved. There were products that were full spectrum, meaning a lot of cannabinoids, broad spectrum and some companies we had single isolates, maybe CBD only or cannabinol (CBN) only, certain formulations. It was kind of a variety and that was tested out in the in the results as well.

 You have to be careful on how any of these companies market their products. They can't make claims. You can't say that this particular product is going to improve your migraines or help you sleep. But you can discuss or kind of market it by saying it is well known in the industry that CBD can be an anti-inflammatory, it can help you with anxiety, it can help you sleep. How they market their own products is up to the individual companies. But they do have to be careful on the verbage. There are companies that are getting warning letters actually coming out and saying what their products are doing without the appropriate proof. And they have not gone down the drug development pathway. And as Jeff had said, they may market themselves as nutraceuticals or over the counter products, direct to consumer, or e-commerce. And so, it's a market that is continuing to develop.

 This study was what we call this real-world. A lot of individuals are taking these products already, and in order to qualify for this study patients had to have been taking a cannabinoid product for 30 days. And if they met inclusion criteria - we originally reached out to 28,000 individuals. The trial included just under 1500 qualified individuals, who then took the products for 30 days.

They journaled, Dr. Aqua looked at their medical history to make sure they met all the criteria, they signed informed consent. And at the end of the study – so 60 days at a minimum being on a cannabinoid - we drew blood and we looked at their liver function tests. Now I can tell you that some of these individuals were on the cannabinoid products a lot longer, 6 months, even 12 months or more. We had a variety of those individuals that were just starting the study for a short period of time or on product, but also included those on CBD products for much longer.

 As Jeff mentioned, we had about 28,000 patients that had the opportunity to be in the trial, and we had over 1400 patients enrolled in the study. We did in fact, discover that many more patients were taking this for medical problems, more than we thought they would be, even though this was, again, a real-world generally healthy population.

We also discovered that when we looked at the increase in liver function tests for those patients that exhibited increased liver function, it was really not significantly increased compared to what the literature supporting other products were, again, taking into effect some of those other products - those were given to patients for pediatric seizure disorders. They were taking sometimes 5 to 10 milligrams per kilogram. In the real-world, patients are not taking that amount. We only had 3 patients that had greater than 3 times the upper limit normal of liver function tests. And in a population that we had, that is not at all greater or significant compared to the general population. And in clinical trials, we generally look at labs that are greater than 3 times the upper limit of normal as something that would be viewed as an adverse event or potentially a significant adverse event. And so, from that standpoint, we were happy to say that we didn't feel that these CBD products, each individual company’s CBD products, led to a significant increase in liver function tests or liver damage that would be associated with that.

 One thing that was really interesting in the study of these 28,000 individuals was that we got a really good history of what the patients felt they were taking the medication for, so what indications, which was really interesting. And also what other medications they were taking in addition to the cannabinoids. So, we have a lot of data based just on that.

It was interesting seeing those combinations and as a pharmacist and as a clinician. Dr. Aqua is really interested in drug interactions and potential drug interactions because these drugs are metabolized through the cytochrome p450 system. There are some warnings out there. There are some contraindications if you have dual metabolism through some isoenzyme 2C19384. We really don't have set recommendations on what to do. I remember when I was doing bone marrow transplant patients when they're going on immunosuppression, and they needed an antifungal. We empirically did a 50% dose reduction based on the potential drug interaction that could occur. Those are some of the questions I think that are out there to what to do in those scenarios. This very large database that we will use to do preliminary studies and follow up studies - and Dr. Aqua will mention maybe a Cohort 2 that we're actually starting this month going forward - continuing the study based on some of these interesting findings and some of the guidance we received back from the FDA when we spoke to them on our results of the study. Very interesting.

 And it's interesting that you have Jeff and I, because Jeff is coming from a pharmacy background and I'm coming from a clinical background. But I'm seeing patients come to the office every day, and they're on these products and a lot of physicians don't understand the endocannabinoid system, they do not understand some of these drug interactions. And as you get more scientists, PhDs, MDs, PhDs in biology and chemistry and pharmacy involved, we can help patients make more informed decisions.

And as Jeff alluded to, we are going to look at Cohort 2. That's going to look at several pieces of data. Number 1, the patients that had elevated liver function tests in the first cohort, we did not have a second liver function test blood drawn. Some of this was due to COVID inability to get the patients to come into the clinical trial office. This was a completely virtual decentralized trial, so Cohort 2, anybody who had elevated liver function tests, we are going to look at doing a second blood draw to see if this was just a spurious random elevation.xz e Z Was it associated with other medications they were on? Did they have alcohol intake a couple days before they had it? So, we're going to try to look at that. And then there's some other data out there looking particularly at men and testosterone production and other liver functions, things like alkaline phosphatase that we have in this database as well.

So, I think out of this second cohort, it was combined data with the first cohort, we're going to have a very large real-world sampling of patients that, as Jeff alluded to, we know that they're on this CBD product for a minimum of 60 days, a lot have been on it for a lot longer. And when we look at the literature, we see random clinical trials that'll provide information that a patient was on 800 milligrams for a week, or a patient was on 1600 milligrams for a month, but we don't have long term data on patients that have had it for a very long time. Except, again, I go back to those pediatric seizure disorders and the work that GW Pharmaceuticals did. But in the real-world, we don't have that longitudinal data. And we hope to add to that database.

 The FDA was very happy that we were doing the trial. They were very interested in individuals trying to bring appropriate data, peer reviewed and somewhat prospective data into the database. They were not critical of the not having the second liver function tests, but they asked questions about that. And when we did the study design, we knew that we were going to be asked questions about that.

 And, certainly with COVID, over the last 14 to 15 months, minimizing the patient's exposure to labs and their possibility of not getting the data that we needed, we had to take that into consideration. But they were giving us the appropriate guidance on that. And we went to start the second cohort, submitted to do further IRB testing on those patients do have elevated liver function tests. And we did get IRB approval to do that, so I think their suggestions were very well received. They have a very large group there that want to help companies and help consumers educate and get the data, so we can kind of catch up. The horse is out of the barn, so to speak. Now the data and the science need to catch up.

 I thought it was a very good meeting. It certainly was a collaborative environment. So this was a liver toxicity study done with the Valid Care platform, looking at liver toxicity, but they were very interested in some of the other work that Dr. Aqua is doing some of the work that that we're doing at the university.

We focus in on some of these products, we look at single dose and multi-dose PK curves, to see how much of the medication is actually being absorbed into the body. We can measure cannabinoids metabolites with some of these products and really give back some of that safety information that the FDA is interested regarding drug development. Some of those preclinical and clinical studies, all these companies, the majority of them have done a lot of work looking at the safety of their products, that they're grass certified and are taken seriously. They're very interested in the science, and I applaud them for being part of this study.

 I do want to give a shout out to Valid Care. I think the Valid Care team has done a really good job at putting together companies and really stressing the importance of getting this information. Patrick McCarthy, who's the CEO of Valid Care, has extensively networked to reach out to these companies and to help them recognize that the research that we're doing and the drug development that they're doing is important to help consumers from both safety and efficacy in the future.

 I think their platform in this COVID environment - it's an app-based platform that they're able to do electronic consent, it's 21 CFR Part 11, decentralized clinical study platform, which is very similar to what the FDA use for some of their COVID-19 trials. I don't think we could have done this with all these companies and with all these individuals. It was a national study, and I believe we had a couple in Alaska as well. So once again, we're using this platform and working with Valid Care for some other studies that we're doing. They have a really good platform.

Editor's note: Jeff Lombardo is a member of the Editorial Advisory Board for 

Co-principal investigators Jeff Lombardo and Keith Aqua discuss the unique patient profiles of the study, future cohorts, and FDA's response to the findings. 