#first in human clinical trials guidelines fda

[sauravchemicals]

The Importance of Active Pharmaceutical Ingredients in Drug Development

Introduction

The role of Active Pharmaceutical Ingredients (APIs) in drug development is often understated, yet it's the cornerstone of any effective medication. These critical components are responsible for the therapeutic effects of a drug, making their quality and efficacy vital. This article delves into the significance of APIs in the pharmaceutical industry, particularly focusing on drug development and manufacturing.

Understanding APIs

APIs are the substances that produce the intended effects in pharmaceutical drugs. They interact with specific biological targets to bring about therapeutic outcomes. In essence, the API is the 'active' element that treats the condition or symptom for which the drug is prescribed.

The Role in Drug Development

In the initial stages of drug development, identifying or synthesizing a potential API is often the first step. This is followed by rigorous preclinical testing in the lab and in animal models to evaluate its safety and efficacy. Once the API shows promise, it moves to clinical trials involving human subjects to confirm its safety and effectiveness.

Quality and Purity

Importance: The quality and purity of an API directly impact the drug's safety and efficacy.

Regulatory Guidelines: To ensure these standards, APIs must meet stringent quality guidelines set by regulatory bodies like the FDA and EMA.

Manufacturing Considerations

APIs can be synthesized through various methods, including chemical synthesis, fermentation, and extraction. Regardless of the method, rigorous quality control is essential. This ensures that the API's purity and potency meet the required standards, which is crucial for the success of the final drug product.

Challenges and Solutions

API drug development is not without its challenges. The increasing complexity of APIs, especially with the advent of biologics, makes the manufacturing process intricate. Additionally, APIs are subject to stringent regulatory requirements, making the development process both time-consuming and costly. However, advances in technology and a focus on sustainable methods are paving the way for more efficient and eco-friendly API production.

The Future of APIs

The pharmaceutical industry is continuously evolving, and APIs are at the forefront of this change. Advances in genomics are paving the way for personalized medicine, where APIs can be tailored to individual genetic profiles. Moreover, the rise of biologic drugs has led to the development of more complex APIs, opening new avenues for innovation.

Conclusion

Understanding the critical role of Active Pharmaceutical Ingredients in drug development can provide valuable insights for stakeholders in the pharmaceutical industry. As the industry continues to evolve, APIs will undoubtedly remain at its core, driving innovations in drug development, personalized medicine, and more.

For those looking to venture into API manufacturing, partnering with an experienced company like Saurav Chemicals can offer invaluable expertise and solutions, helping you navigate the complexities of API drug development and manufacturing.

#Active Pharmaceutical Ingredients #API manufacturing #API drug development #API drug manufacturing

[altabrisagroup2]

Demystifying Regulatory Compliance for Biotechnology Products

Introduction

Biotechnology products, which include biologics, gene therapies, and cell-based therapies, are at the forefront of medical advancements, offering new treatment options for various diseases. However, due to their complex nature, ensuring regulatory compliance for biotechnology products can be challenging. In this article, we will demystify regulatory compliance for biotechnology products by exploring the key aspects and considerations involved in meeting regulatory requirements.

Understanding the Regulatory Landscape

The first step in ensuring compliance for biotechnology products is to understand the regulatory landscape. Different countries have specific regulatory agencies and guidelines governing the development, manufacturing, and marketing of biotechnology products. In the United States, for example, biologics are regulated by the US Food and Drug Administration (FDA), while the European Medicines Agency (EMA) oversees biologics in the European Union.

Preclinical and Clinical Development

Compliance with preclinical and clinical development requirements is essential to demonstrate the safety and efficacy of biotechnology products. This involves conducting comprehensive preclinical studies in animal models and well-designed clinical trials in human subjects. Following Good Laboratory Practice (GLP) and Good Clinical Practice (GCP) guidelines ensures the reliability and integrity of data generated during these phases.

Quality Control and Manufacturing

Biotechnology products are often complex and sensitive to manufacturing processes. Compliance with Good Manufacturing Practice (GMP) is critical to ensure the consistency and quality of the final product. Manufacturers must implement robust quality control measures to monitor product attributes and address potential deviations. Check here pharma compliance consulting

Regulatory Submissions

Compliance with regulatory submissions involves preparing and submitting dossiers containing detailed information about the biotechnology product's development, manufacturing, safety, and efficacy data. These submissions may include Investigational New Drug (IND) applications, Biologics License Applications (BLAs), or Marketing Authorization Applications (MAAs), depending on the regulatory pathway.

Risk Management and Pharmacovigilance

Biotechnology products often carry unique safety considerations. Compliance with risk management and pharmacovigilance requirements involves continuous monitoring of safety data and taking appropriate risk mitigation measures when necessary. Post-market safety reporting and signal detection are essential to ensure patient safety.

Post-Market Surveillance

Compliance with post-market surveillance is essential for biotechnology products to assess their long-term safety and effectiveness. Manufacturers must continue to collect and analyze real-world data to monitor the product's performance in the broader patient population.

Labeling and Advertising

Compliance with labeling and advertising regulations ensures that the product's information provided to healthcare professionals and patients is accurate, comprehensive, and in line with regulatory requirements. Clear and transparent labeling is essential for informed decision-making.

Compliance Audits and Inspections

Regulatory authorities may conduct compliance audits and inspections to assess a company's adherence to regulatory requirements. Being prepared for such audits and promptly addressing any findings is crucial to maintain compliance.

Continuous Improvement

Compliance for biotechnology products is an ongoing process. Manufacturers must continuously improve their processes, address emerging issues, and update their practices in response to new regulations and scientific advancements.

Conclusion

Regulatory compliance for biotechnology products is a complex and dynamic process, but it is essential to ensure patient safety and the availability of innovative therapies. By understanding the regulatory landscape, conducting thorough preclinical and clinical development, implementing robust quality control and manufacturing processes, and complying with post-market surveillance requirements, stakeholders in the biotechnology industry can navigate the regulatory pathway successfully. Continuous improvement and proactive engagement with regulatory authorities are key to staying compliant and bringing safe and effective biotechnology products to patients worldwide.

[happy-smile-flowers]

Accelerating New Drug Development: The Role of Radioisotope Labeling

In drug development, Radioisotope labeling has become a powerful tool. It provides a means to track the fate of drugs in the body and helps researchers to better understand the metabolic processes and potential toxicity of new compounds. So, scientists can design more effective and safer drugs, reducing the risk of adverse effects and increasing the likelihood of success in clinical trials.

Isotopes are atoms of the same chemical element with different masses due to the presence of different neutron numbers in the nucleus, and there are light and heavy isotopes; based on physical properties, isotopes can also be classified into two forms: radioactive and stable. Radioisotope labeling technology is a very useful tool in the process of new drug development, and Medicilon offers radioisotope services.

Based on physical properties, isotopes can be classified into two forms: radioactive and stable. Radioactive isotopes (e.g. 3H, 14C) undergo their decay process and radiate radiation energy, are unstable, and have physical half-life; stable isotopes are non-radioactive, have stable physical properties, exist in nature in a certain proportion (abundance), are harmless to the human body, and can be labeled into drug molecules by chemical synthesis and tracked and detected by instruments such as gas and liquid quality.

1, The reason why radioisotopes are widely used.

Radioisotopes are widely used for active material tracing mainly depending on two most important characteristics:

(1) homogeneity with the material being traced, i.e., a high degree of consistency in chemical and biological behavior between the radionuclide and its non-radionuclides of the same element, without disturbing and disrupting the equilibrium of physiological processes in vivo and in vitro;

(2) Distinguishability with the traced material, where the nucleus of the radionuclide continuously decays and emits rays that can be detected by the radiosonde, thus enabling the quantification and localization of the marker.

In addition, radioisotope tracer technology has the advantages of high sensitivity, high specificity, wide applicability, and simple detection method, so it has been widely used in drug ADME research, and the U.S. FDA has long taken the pharmacokinetic data of radioisotope labeled drugs after administration as an important basis for the safety evaluation of new drugs, and has formulated relevant guidelines.

2, The direction of radioisotopes in drug development

In terms of quantitative sensitivity, radioisotope-labeled compounds are more sensitive than stable isotope markers, and the measurement of radioactivity is not affected by non-radioactive impurities and chemical states, thus making quantitative analysis easier and the results more accurate. In addition to solving analytical problems that cannot be solved by conventional analytical methods, radioisotope-labeled compounds can more importantly be used as tracers to study the distribution, metabolism, efficacy, and mechanism of action of drugs in vivo, providing an important basis for the pharmacokinetic study of drugs, and providing methods for the development of innovative drugs.

3, Choice of radioisotope labeling position

Before the preparation of labeled drugs, the first step is to select the appropriate isotope as the labeling element and decide on the labeling position. The labeled drug used for tracer study should make the labeled atoms represent the whole molecule of the drug in the organism as much as possible and should pay attention to the possible changes of the drug in the body. The structure of the drug molecule, the half-life of the isotope, the energy of the radiation, the ease of introducing the labeled atom, and the special requirements of the tracer test should be taken into account when choosing the isotope to be used as the labeled atom. The most commonly used isotopes are 14C, 3H, and 35S; sometimes 32P and 131I are also used.

As the most commonly used radionuclide, 14C is usually labeled on the skeleton structure of molecules, and its labeling sites are more stable; 3H is prone to exchange with 1H in the surrounding environment, resulting in a decrease in a specific activity, so it is less stable than 14C; in addition, 3H has a more obvious isotope effect compared with 14C, which also limits its application to some extent. However, in general, in tracer experiments, the errors caused by isotopic effects are often within the experimental allowable errors and can be neglected. In addition, considering that the synthesis of 3H markers is relatively simple, 3H markers are also often chosen as tracers when they can meet the experimental requirements.

In addition to the above, computer-assisted metabolite prediction (CAMP) techniques can be used in the selection of labeling sites to predict stable sites in the molecular structure of compounds. In general, labeling of C atoms on aromatic or alicyclic rings in the molecular structure should be considered first, while labeling at active sites such as carboxyl, hydroxyl, sulfhydryl, amino, and imino groups should be avoided as much as possible. This is because once these unstable groups are separated from the parent compound, the ability to trace the parent drug and major metabolites is lost. In addition, the labeling site should be far away from the chemical bond-break location to avoid the effect of isotope effect. If the parent compound generates 2 important metabolites simultaneously due to chemical bond breakage during metabolism, a dual-labeling technique can be considered for parent compound labeling.

Medicilon offers radioisotope analysis services for labeling experiments in the drug development process using radioisotopes such as 3H, 14C, 32P, 33P, 125I, and 35S.

#radioisotope #medical

[ccrpsorg]

2023 Updates for Clinical Research Associates and Clinical Research Monitors

Common clinical trial guidelines used for monitors are designed to ensure the safety and accuracy of the data collected. These guidelines help to make sure that all participants in the trial are treated fairly and ethically, as well as ensuring that the results of the trial will be useful for medical research.

One important guideline is that the monitor must be independent from both the sponsor and investigator. The monitor should have no interest in or influence on the study's outcome, and must have complete access to any documents or records related to conducting the trial. Additionally, they are responsible for ensuring that all protocols are followed correctly, data is correctly recorded and stored, and any adverse events or reactions reported accurately and promptly.

Another key guideline is that monitors must act in accordance with Good Clinical Practice (GCP) guidelines established by International Conference on Harmonization (ICH). GCP outlines procedures for clinical trials involving human subjects so that ethical practices can be maintained throughout a study. It covers many topics including informed consent, protocol review, quality assurance/monitoring, investigator qualification requirements, patient safety procedures, and data verification methods.

Additionally, monitors may use other standards such as The Code of Federal Regulations (CFR), which is used by US Food & Drug Administration (FDA) to regulate drugs; International Committee on Harmonization (ICH) E6R2 ethical guidelines; European Medicines Agency’s Guidelines on Good Clinical Practice (GCP); World Health Organization’s International Ethical Guidelines for Biomedical Research Involving Human Subjects; or local regulations specified by each country’s health ministry.

Overall, these guidelines help to ensure that monitors remain impartial during a clinical trial - this helps to protect participant safety as well as providing reliable data for researchers later down the line.

Clinical research monitors are responsible for ensuring the safety of participants in clinical trials and the accuracy of data collected. In 2023, there have been several updates to guidelines for clinical research monitors that they should be aware of.

The United States Food and Drug Administration (FDA) has released Clinical Trials Guidance Documents that provide advice on the conduct of clinical trials, good clinical practice, and human subject protection. These documents outline the standards that must be met in order to ensure a safe and ethical trial environment.

Clinical research associates (CRAs) play a key role in medical research, ensuring that clinical trials are conducted according to the highest standards of quality, safety and ethics. In light of this importance, the U.S. Food and Drug Administration (FDA) has recently released new guidelines for CRAs conducting clinical trials. These guidelines provide an important framework to ensure that all research is conducted responsibly and ethically while protecting participants’ rights and safety. The FDA’s new guidelines focus on three main areas: data security, participant monitoring protocol, and communication with sponsors.

First, the FDA has established stringent data security measures to protect trial participants’ information during all stages of the trial process. This includes measures such as encryption of sensitive data, physical access control systems for secure areas where information is stored or processed, and regular backups of critical data sets to prevent any potential losses due to cyber-attacks or system malfunctions.

Second, the FDA requires that participation by CRAs in clinical trials include appropriate monitoring protocols designed to minimize risks associated with various trial procedures. This may include frequent communication with study sponsors about changes in protocol or patient status; close observation of trial participants; review and approval of all research documents before their use; scheduling regular safety assessments; and maintaining accurate records of all activities associated with each trial phase.

Finally, CRAs must maintain open communication channels with sponsors throughout the duration of a clinical trial in order to promptly report any changes in protocol or patient status that may require further review or approval from sponsors. Additionally, CRAs need to be trained on how to effectively communicate any necessary updates or potential issues related to regulatory compliance so they can ensure effective oversight over the entire course of a study period.

The FDA's new clinical trial guidelines provide an essential reference point for CRAs responsible for conducting medical research safely and ethically while protecting participants' rights and well-being. With these comprehensive guidelines in place, CRAs now have an even greater responsibility than ever when it comes to ensuring the success of health-related studies around the world.

Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers 3/15/2023

Considerations for the Design and Conduct of Externally Controlled Trials for Drug and Biological Products 1/31/2023

Clinical Investigator Administrative Actions — Disqualification 12/01/2022

Acute Myeloid Leukemia: Developing Drugs and Biological Products for Treatment 10/17/2022

Tissue Agnostic Drug Development in Oncology 10/17/2022

Characterizing, Collecting, and Reporting Immune-Mediated Adverse Reactions in Cancer Immunotherapeutic Clinical Trials 10/17/2022

Ethical Considerations for Clinical Investigations of Medical Products Involving Children 09/23/2022

Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drug and Biological Products 09/08/2022

We must always review the Handbook for Good Clinical Research Practice (GCP), which provides guidance on implementation of GCP standards. Additionally, the International Council for Harmonisation (ICH) has published Efficacy Guidelines which address design, conduct, safety and reporting of clinical trials.

2023 Good Clinical Practice Guidelines for Clinical Research Associates:

Clinical research associates must stay up-to-date on the latest clinical research regulations, guidance documents, and technology advancements in order to ensure ethical and compliant clinical trial management.

Clinical research associates must establish effective communication with all members of the research team to facilitate the exchange of information regarding study updates, timelines, and protocols.

Clinical research associates are responsible for performing accurate data entry into relevant databases or case report forms (CRFs) as part of their role in documenting results from clinical trials.

Clinical research associates must ensure that informed consent is obtained from all participants in accordance with local regulations and international ethical standards.

Clinical research associates must be knowledgeable about relevant In Vitro Diagnostic (IVD) device regulations and requirements for providing evidence of conformity, accuracy, and effectiveness prior to use in a study.

Clinical research associates should create detailed visit plans for each participant in order to maximize the efficiency of visits to investigator sites during a study without compromising data quality or patient safety.

Clinical research associates should conduct regular quality assurance (QA) activities such as source document verification (SDV), query resolution, audit trails, monitoring reports review, reconciliation activities etc., ensuring data accuracy throughout the course of a study period.

During audits or inspections conducted by regulatory authorities or ethics committees, clinical research associates must be prepared to present comprehensive documentation demonstrating compliance with GCP principles and local regulations governing clinical trial conduct.

The European Medicines Agency (EMA) has also released a Clinical Trials Regulation which harmonises processes for assessment and supervision of clinical trials throughout the EU. This regulation outlines requirements to ensure patient safety during a trial as well as evaluation procedures for new drugs or treatments being tested in a trial setting. Finally, The EQUATOR Network provides study protocols such as SPIRIT and PRISMA-P; diagnostic/prognostic studies such as STARD and TRIPOD; case reports such as CARE; extensions; clinical practice guidelines such as AGREE; all aimed at enhancing quality and transparency in health research publications.

In 2022, the US Food and Drug Administration (FDA) released new clinical trial guidelines that emphasize patient safety. The guidelines mandate that all clinical trials must adhere to a rigorous set of standards in order to ensure patient safety and efficacy.

The new guidelines require research teams to obtain written informed consent from participants prior to initiating any study activity. Abuse of animals is prohibited, and investigators are expected to use only those treatments that have shown potential benefit in animal studies. Additionally, researchers must report any adverse events or reactions during the course of the trial and ensure proper follow up care for affected individuals.

Furthermore, the FDA requires that research teams perform rigorous safety monitoring throughout the course of the trial. Regular data analyses and reviews must be conducted to identify potential risks and unexpected results, which must be reported in real time. Additionally, the FDA requires research teams to implement a system for tracking participant adherence to protocols, including collecting data on missed doses, changes in medication regimens, and other protocol violations.

The FDA also mandates more frequent reporting of results throughout the course of clinical trials. They require researchers to share interim results with stakeholders every six months or whenever significant changes occur in study design or purpose. These reports should include key findings as well as basic information about participant demographics and outcomes associated with each treatment arm.

Finally, the FDA has increased their emphasis on transparency by requiring researchers to disclose detailed information regarding sponsoring organizations and conflicts of interest associated with each study before it begins. This includes information related to payments made by sponsors as well as nonmonetary benefits received by investigators or other individuals associated with the trial.

By 2023, additional provisions will be added to these regulations including enhanced requirements related to diversity among participants; strengthened criteria for evaluating ethical considerations such as protection from harm; expanded definitions related to economic conflict-of-interest disclosure; greater emphasis on appropriate risk/benefit ratios; improved reporting of results utilizing standardized metrics; increased focus on study protocol adherence; enhanced data sharing practices; clear criteria for determining when further review is needed due health concerns; specified mechanisms for measuring patient quality-of-life outcomes; increased accountability through stronger recordkeeping systems; enhanced guidance around informed consent forms; improved methods for monitoring compliance; greater attention paid towards reviewing unpublished manuscripts related to clinical trials; expansion of proposed preventative measures targeting financial misconduct issues such as fraud detection systems; improved oversight mechanisms using Artificial Intelligence technologies such as natural language processing (NLP); and additional efforts aimed at improving public understanding around clinical trials through better communication strategies between sponsors and patients alike.

Stay up to date on clinical trials and your annual ICH GCP certification through one of the most comprehensive courses in the industry.

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[innonurse]

Verkko is an on-demand genome assembly software created by the NIH

- By InnoNurse Staff -

Researchers at the National Institutes of Health (NIH) have created and released an innovative tool for assembling genuinely entire (i.e., gapless) genome sequences from a range of species. Verkko, which means "network" in Finnish, is software that aims to make the process of assembling whole genome sequences more economical and accessible.

Read more at National Human Genome Research Institute (NHGRI)

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Other recent news and insights

Neurotechnology: Spinal cord stimulation increases arm movement immediately after stroke (UMPC)

RxE2 launches Diversity Now, the first protocol to achieve diversity in clinical trials in accordance with the FDA Guidelines for Race and Ethnicity Diversity Plans is now available (RxE2/PRNewswire)

#nih #medtech #health tech #genomics #dna #genome sequencing #biotechnology #biotech #neuroscience #brain #stroke #spinal cord #rxe2 #fda #diversity #clinical trials

[utheversblog]

How to take nmn powder? Directions to use

Nicotinamide mononucleotide (NMN) is a potent anti-aging, weight-loss, energy-improving, cardiac health, vision-improving, and diabetes component. It also works by preventing oxidative stress and other forms of cell damage. nmn powder wholesale provides a number of health advantages, but its dose forms are not subject to any governmental rules. Nevertheless, studies on rats have established its safety for human usage, and human clinical trials are currently being conducted. Let's look at the ideal NMN dosage for humans, the NMN cycle, how to take NMN powder, and the optimal time of day to take NMN.

When should I take my NMN supplement?

The appropriate dose of NMN has not yet been determined because it has not received FDA or European Medicines Agency approval (EMA). We thus used trial and error, and research using animal models demonstrates that taking NMN twice daily is excellent. It is advised that taking one 125mg capsule twice a day will provide a sufficient energy boost.

Ways to consume NMN powder

NMN powder can be used sublingually till problems are rectified. To increase absorption, it can also be directly ingested together with some mild yoghurt.

When should I use NMN Powder?

The morning is the ideal time to take NMN supplements. We think that taking NMN first thing in the morning is advantageous for carrying out daily chores because it is a significant source of immediate energy.

Daily dose of NMN

Dr. David Sinclair, a well-known figure in the NMN sector, consumes 1g, or 1000mg, of NMN every day. One recent study demonstrates that consuming 2000 mg of NMN daily is safe and beneficial. Another Japanese study found that taking 125mg of NMN twice daily for eight weeks is beneficial to health. Information on the long-term use of NMN is currently lacking.

The suggested dosage for nmn is described in the following table.

Age/Weight

NMN Dosage

30-40 years/30kg-40kg

200mg-400mg/day

40-50 years/50kg-60kg

400mg-600mg/day

Above 50 years/80kg

800mg-1200mg/day

Effepharm adheres completely to USP and FDA guidelines to ensure production is of the highest possible calibre. Genuine Uthever is provided by EffePharm, and Intertek, a global third party, has verified its purity.

The market's highest purity product, Uthever® from Effepharm, has less contaminants, especially endotoxins. Our customers in the United States and Europe love Uthever®.

We significantly reduced its hygroscopicity and temperature sensitivity with Effepharm's NMN, enabling it to be stored at standard room temperature. We've used contemporary pharmaceutical technology to create controlled-release and sustained-release NMN formulations in an effort to increase its bioavailability. Please get in touch with us if you'd want more details as soon as new, inventive forms are created.

How can we restore our NAD+ levels? Since NAD+ exists naturally, our cells already possess the machinery needed to produce it; they only require the required biochemical elements. Like an assembly line in a factory, our cells create molecules, with each part serving as a precursor to the next. Nicotinamide mononucleotide is the name of the biological precursor to NAD+ (NMN). NMN can be taken orally, unlike NAD+ itself, and can therefore be used as a supplement to increase NAD+ levels.

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[myblckcty]

Curtis Powells | Orion Research Solutions FSU, LLC

Join My Black City in Celebrating and Supporting Curtis Powells | Orion Research Solutions FSU, LLC. We Shine Brighter Together. #MyBlackCity https://myblackcity.org/curtis-powells-orion-research-solutions-fsu-llc/?feed_id=15079 >> When drugs are first placed on the market, there are so many unknowns of how the drug will affect a black person. We need to be as prepared as possible. >> Pharmaceutical Industry How did your industry get started? My industry got started when the Public Health Services began working with Tuskegee Institute in 1932. The very first study recorded in history was syphilis. In this study, 600 black males, were studied throughout 40 years. During this period, these men were never given adequate treatment. When treatment became, available patients weren’t adequately informed about the extent of the study. In 1972, the study was deemed ethically unjustified and ceased immediately. The patients that participated in this study, including their families, were given reparations. This event was the catalyst to birth the Declaration of Helsinki. The Declaration of Helsinki set the expectations of ethical principles for human experimentation in the medical community. To protect people’s rights, even further patients were required to sign an informed consent document that explains the clinical research. The safeguards that have been enacted are the main reason that I have the job I have today. What I do ensures the FDA guidelines are followed and those principles are upheld when conducting any medical study. There is an overabundance of distrust in the black community toward medical professionals because of the Tuskegee experiments. Why is it important for black people to continue to participate in medical research? Drugs used to be developed in a broad spectrum, one size fits all, and now they are being created more to be precise to genetic makeup. Drugs affect people differently because of the individual’s genetic makeup. Black people typically refuse participation in medical research studies due to the negative stigma of previous experiences. Regardless if black people participate in research trials, drugs are still being created without knowing the effects the drugs could potentially have on black people. With 90% of medical research being conducted on white people, there is insufficient data on how these drugs can affect black people. Black people wind up getting a prescription for a drug that can hopefully treat a condition, but could also be ineffective, or have adverse side effects. It is critical for people of color to get involved in clinical research as a patient, or investigator. Our young people need to understand how the profession works, as well as our older generations. At the end of the day, your doctor is going to write you a prescription thinking the drug will work for you, disregarding the potential drug not being tested on a person of color. When drugs are first placed on the market, there are so many unknowns of how the drug will affect a black person. We need to be as prepared as possible.

#HealthandWellness

[needclick7]

Don’t Fall For This Stretching Scam

The Dane succeeded in getting Tsitsipas out of his comfort zone on the baseline, sending his tall opponent to the web with drop factors and stretching him wide off the courtroom with deep cross-court balls. The firm is the UK’s second-biggest water agency, serving 4.8 million houses and businesses in England and Wales, stretching from mid-Wales to Rutland and from north and mid-Wales south to the Bristol Channel and east to the Humber. Most of us don’t drink sufficient water each day, but it surely is crucial for our bodies to work correctly. “That 스웨디시 don’t want. August 23, 2010 - US District Judge Royce C. Lamberth issues a preliminary injunction that prohibits the federal funding of embryonic stem cell analysis. July 19, 2006 - President Bush vetoes the embryonic stem-cell research bill passed by the Senate (the Stem Cell Research Enhancement Act of 2005), his first veto since taking office. June 20, 2007 - President Bush vetoes the Stem Cell Research Enhancement Act of 2007, the third veto of his presidency. September 9, 2010 - A 3-choose panel of the US Court of Appeals for the DC Circuit grants a request from the Justice Department to carry a temporary injunction that blocked federal funding of stem cell analysis.

November 22, 2010 - William Caldwell, CEO of Advanced Cell Technology, tells CNN that the FDA has granted approval for his firm to begin a clinical trial utilizing cells grown from human embryonic stem cells. 1998 - President Bill Clinton requests a National Bioethics Advisory Commission to check the query of stem cell research. April 2014 - For the primary time scientists are ready to use cloning applied sciences to generate stem cells that are genetically matched to grownup patients,in keeping with a study revealed within the journal, Cell Stem Cell. October 2014 - Researchers say that human embryonic stem cells have restored the sight of several practically blind patients -- and that their latest research shows the cells are protected to make use of long-term. May 2013 - Scientists make the primary embryonic stem cell from human skin cells by reprogramming human pores and skin cells again to their embryonic state, based on a examine printed in the journal, Cell.

You will make errors as you attempt to love and reassure and comfort your pals and household within the midst of their loss. 2. Try out the newly deployed LocalityHealer, which was not yet running as a daemon. In our testing, our favourite treadmill is Bowflex's Treadmill 22. Built like an absolute tank, this treadmill has a 4-horsepower motor, a 22-inch-large by 60-inch-long working path and Comfort Tech deck cushioning that helps absorb shock even at higher working deck speeds. Analyzing the activity helps them to understand the mysterious Martian inside and apply this analysis to learn the way other rocky planets, together with our personal, are formed. Additionally, it helps to search out mattresses with one of the best type of pressure-relieving qualities and correct spinal help for stomach sleep -- in addition to cooling properties for scorching sleepers and as many extras as you could find. And it could be properly if nurses would watch these (so-called) “fancies” carefully. The software program works on gadgets as old because the Apple Watch Series 3, though some options might require newer fashions. The music: Tonal has a terrific collection of native music in several genres, or you can connect the gadget to your Apple Music account.

2000 - The National Institutes of Health (NIH) points guidelines for the usage of embryonic stem cells in analysis, specifying that scientists receiving federal funds can use solely further embryos that may otherwise be discarded. 2000 - During his marketing campaign, George W. Bush says he opposes any analysis that entails the destruction of embryos. July 11, 2002 - The President's Council on Bioethics recommends a 4-yr ban on cloning for medical analysis to allow time for debate. February 27, 2002 - For the second time in two years, the House passes a ban on all cloning of human embryos. According to a report printed within the Lancet, the researchers transplanted stem cells into 18 patients with extreme imaginative and prescient loss on account of two forms of macular degeneration. This compact Anker charger has two comparatively high power USB-C ports, sufficient to deliver 27 watts to my laptop. It plugs into the wall with flip-out energy prongs and one other flip-out USB-C connector, so you do not need a cord. February 15, 2022 - A US woman turns into the third recognized individual to enter HIV remission, and the primary mixed-race lady, thanks to a transplant of stem cells from umbilical cord blood, based on research offered at a scientific convention on Retroviruses and Opportunistic Infections.

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[ucsdhealthsciences]

What Will it Take to Create a Vaccine for COVID19?

April 29, 2020, 3:30 p.m. — One of the big challenges in navigating the COVID-19 crisis is the novelty of the virus. Because it’s so new, we don’t have any way to prevent infection — and without a vaccine, there’s no telling how long the pandemic will last. So what will it take to get a COVID-19 vaccine available to the public? And why is it taking so long?

What we know about COVID-19

Viruses operate by attaching themselves to living cells in our body and injecting their genetic material, called RNA. The RNA hijacks the machinery of the cell to replicate itself, producing copy after copy of the virus, which eventually explode out of the cell to go in search of new cells to infect. In the case of SARS-CoV-2, the virus primarily attacks the epithelial cells lining the lungs. In the lungs, the fight between your immune system and the virus can cause inflammation, cell death and excess fluid, a combo that leads to pneumonia. Sometimes, when the infection is really bad, patients end up with acute respiratory distress syndrome, or ARDS, when their lungs are so clogged up that their bodies aren’t able to absorb enough oxygen and they really struggle to breathe.

There’s also evidence that the virus, and/or the inflammation it causes, might be having effects on other organs in the body, causing long term complications including brain, liver, kidney, and heart damage and increased risk of blood clots.

Protection against a viral illness is conferred by antibodies, produced by the immune system in response to exposure to the virus. In most cases, contracting the virus gives the immune system the information it needs to produce those antibodies, which can then activate and fight the virus on the next exposure.

What it takes to develop a vaccine

Vaccines take advantage of our natural immune system response to stimulate antibody production against a disease using killed or weakened versions of the pathogen that don’t make us sick. This makes us immune to the disease without ever having to contract it.  

The first step in creating a vaccine is to identify a good antigen to target. These molecules represent portions of the virus’ structure that don’t cause illness by themselves but do activate the immune system to produce the correct antibodies. These antigens are then produced in large quantities by cells in Petri dishes before being purified and, if necessary, the virus is inactivated or killed so it can be safely injected. Finally, the antigen is mixed with adjuvants, to help enhance the immune response to produce stronger immunity, alongside preservatives and stabilizers to give the vaccine a long shelf life and allow for multiple doses from the same vial.

Once a vaccine has been created, it has to be extensively tested: first in animal models, and eventually in human beings. This process goes through three phases, to be sure that the vaccine is safe and effective, and to determine what dose should be administered to patients. It takes a lot of testing to be sure that the vaccine is safe in children, adults, pregnant people, and the elderly. And not every vaccine is recommended for every person. Different governments have to balance cost, risk, efficacy, and public health concerns before deciding whether or not they should add a new vaccine to the standard vaccination list.

Usually, it takes 10 to 15 years to develop a vaccine and get it approved by the FDA for use in patients. The exception are seasonal vaccines, like the flu vaccine. Because the flu virus is tracked year-round by scientists, and because the manufacturing process is kept the same year-to-year, researchers are able to use the same foundation for each year’s vaccine and simply replace the antigen with the new virus.

In the case of SARS-CoV-2, because of the high rates of infection and novelty of the virus, it seems critical that we get a vaccine ready quickly, but it’s not as easy just swapping in a new antigen. Thanks to a lot of technological advancement in recent years, and the large number of industrial and academic researchers working on this problem, we’re moving faster than ever toward a vaccine solution for COVID-19.

What’s already happening on the vaccine front?

The SARS-CoV-2 genetic sequence was published on January 11, 2020, allowing for a global flurry of vaccine development, and the first vaccine entered human clinical trials on March 16. By April 8, 115 vaccines candidates were being tested by academic research institutions and industry companies, with 78 of those candidates being close to formal testing. Several of those have already advanced into clinical testing, with several others hoping to follow within the next several months.

The rapid speed of vaccine development is thanks to a wide diversity of technology platforms, testing a variety of potential sources for stimulating the immune response, including peptides, viral vectors, recombinant proteins, and nucleic acids (DNA and RNA). Researchers are also working to develop adjuvants that will produce the most effective vaccines. Most of these vaccines are being tested in the United States and in China, with some development in Europe, Australia, and other areas in Asia.

What we still need to know and do

We still need to figure out some key details about the SARS-CoV-2 virus. One big question that we haven’t answered yet is whether or not exposure to the virus, or to viral antigens, is enough to generate immunity to the virus. The evidence so far suggests that people who have contracted COVID-19 are protected against reinfection, at least temporarily.

Some cases have indicated that patients who experience a more severe infection of the virus may have more antibodies against it, which may provide better protection against future illness. But it’s still unclear if contracting the virus provides any lasting immunity against it, or how long that immunity might last. At this point, virologists believe that immunity is limited; after 1 to 2 years, patients may be susceptible to a new infection, and require a vaccine to protect against it.

Another question is whether or not COVID-19 is at risk of mutating to become more deadly. At this stage, we just don’t know enough about the virus and its behavior to be certain one way or the other, though some experts doubt that there is a high risk of this happening.

Until some of these vaccines have gone through further clinical testing, we won’t know which ones are actually viable candidates for the public. Part of the challenge is the fact that most vaccines require years of testing in the community, where trial participants receive the vaccine or receive a placebo and then go about their daily lives to see if they end up contracting the virus. Because of the drastic impacts of COVID-19 on our lives and economy, some scientists are suggesting that we consider clinical trials where healthy volunteers are given the vaccine and deliberately exposed to SARS-CoV-2 to see how effective the vaccine might be. This could shave months off the development timeline, but is highly controversial due to the obvious risks for trial participants.

So when will we have a vaccine?

With all of these projects underway, scientists think a vaccine may be approved for emergency use by the FDA as soon as 2021. “Emergency use” means that a vaccine has been tested in humans and found to be effective at preventing infection, but hasn’t been subjected to the full, rigorous scrutiny of a traditional vaccine. It will take more time for all of this extensive testing to be completed — likely several more years.

Despite recent technological advances, this means it will still be at least a year before we have a viable vaccine. With that in mind, the CDC and other public health officials continue to recommend that we follow physical distancing, hand washing and mask-wearing guidelines. It’s important that we continue to work together to protect the health of our friends, family, and community by following stay-at-home recommendations as doctors and scientists work not only on developing a vaccine, but also at better understanding how the virus works and figuring out the most effective ways to treat it.

For more information on what we’re doing at UC San Diego Health, please visit health.ucsd.edu/COVID

— Alison Caldwell, PhD, Bigelow Science Communication Fellow

#covid-19 #covid 19 #novel coronavirus #coronavirus #sars-cov-2 #vaccine #immunology #infectious disease #public health #clinical trials #vaccine protocol #vaccine production #stay at home #flatten the curve #pandemic #hand washing #hand hygiene #shelter in place #self quarantine #quarantine #social distancing #science #medicine #academic medicine #ucsd #uc san diego

[testkitscredencemedicure]

Latest Management Strategies for Hospitalized COVID-19 Patients

The disease spectrum of COVID-19 is very wide. On the one hand are the asymptomatic or mildly symptomatic patients and on the other hand are patients who are fighting for their lives in the intensive care units. A significant number of hospitalized patients undergo severe inflammatory reactions triggered by SARS-CoV-2. Besides supportive therapy, more aggressive treatment strategies are being increasingly used with variable degrees of success.

Blood Purifying Devices

Extracorporeal blood purification (EBP) is a treatment in which blood from a patient is passed through a device (e.g. a membrane or a sorbent) in which a solute (waste products, toxins) and possibly water are also removed. When fluid is also removed, replacement fluid is added. EBP is used primarily in patients with renal failure (Renal Replacement Therapy-RRT). More than twenty years ago, it was seen that RRT could also remove inflammatory mediators from the plasma of septic patients. A survival benefit with hemofiltration was also noted later. Hence, started the use of blood purification as a treatment for human septic shock.

The role of cytokine storm and hyper inflammation, on the severity of COVID-19 patients has been well corroborated in different studies. In an article published in Intensive Care, Ruan et al documented high concentrations of inflammatory biomarkers like C- reactive protein, ferritin and IL-6 in COVID-19 patients who died. They concluded that COVID-19 mortality may be due to virus activated “Cytokine Storm Syndrome” or fulminant myocarditis.

Blood purification devices have now been given permission for use in severe cases of COVID-19 in a number of countries. One brand of blood purifying devices, CytoSorb, was used to treat more than seventy critically ill COVID-19 patients and specifically added to Coronavirus treatment guidelines in Italy and Panama, March 25, 2020. The use of CytoSorb has now begun in seriously ill COVID-19 patients who have cytokine storm and life threatening complications such as Acute Respiratory Distress Syndrome (ARDS), in Italy, China, Germany and France. Preliminary data of the seventy patients tested, shows that there is a marked reduction in Cytokine storm and inflammation, improved lung functions, weaning from mechanical ventilation and a reversal of shock.

CytoSorb is now specifically recommended in the Italy Brescia Renal COVID Task Force Guidelines for treating patients with severe COVID-19 infection and stage 3 renal failure on continuous RRT, published in Italian Society of Nephrology website. Blood purification in COVID-19 infections is also recommended to treat Cytokine Storm by the National Health Commission in China. This technology has been used in thousands of Extra Corporeal Membrane Oxygenation (ECMO) treatments to date, in non COVID-19 patients around the world.

On April 10, 2020, US FDA gave emergency use authorization (EUA) for a pair of Blood Purification Systems to treat adult COVID-19 patients admitted in ICU. The EUA applies to Trumo BCT Inc’s Spectra Optia Apheresis and Marker Therapeutics AG’s Depuro D2000 Adsorption Cartridge. On April 13, 2020 it gave EUA for the CytoSorbent System too.

Mesenchymal Stem Cell Transplantation (MSC)

Umbilical Cord derived Mesenchymal Stem Cells (MSCs) have been used safely and effectively for immune mediated inflammatory diseases such as Graft Versus Host Disease (GVHD) and Systemic Lupus Erythematosus (SLE). MSCs play a positive role in two ways, by immunomodulation and by their ability to differentiate. Immunomodulatory actions are related to secretion of cytokines and because of the direct interactions with immune cells. The immunomodulatory effects are further enhanced by the activation of Toll-Like Receptors (TLR) in MSCs by pathogen associated molecules such as Lipopolysaccharides (LPS) or single stranded RNA from viruses like SARS-CoV-2.

The first step in the pathogenesis of COVID-19 is the entry of SARS-CoV-2 into human cells by attaching to Angiotensin Converting Enzyme-2 (ACE-2) receptors by its spike proteins. A research team from Germany revealed that cellular serine protease TMPRSS2, for SARS-CoV-2 Spike Protein priming, is also important for host cell entry and spread.

ACE2 receptors are present widely on tissues in the body, like type 2 Pneumocytes of lungs, kidney, intestines, capillary endothelium etc. However, the immune cells such as T and B lymphocytes and macrophages, in the bone marrow, lymph nodes, thymus, and the spleen, are all negative for ACE-2 receptors. MSCs are also ACE-2 receptor and TMPRSS2 negative. This makes them immune to SARS-CoV-2. This is the basis of using them in severe COVID-19 infections.

The viral infection causes a total failure of function of lymphocytes and almost the whole immune system. Several studies have reported lymphopenia and high levels of C-reactive protein in COVID-19 patients with severe infections. MSCs play a role by reversing the lymphocyte subsets, mainly through dendritic cells. The interactions of MSCs with the dendritic cells leads to a shift of the immune system from T helper 1 to T helper 2 type of responses.

After entering the human body through the intravenous route, part of the MSCs accumulate in the lung. There, they probably improve the microenvironment, protect alveolar epithelial cells, prevents pulmonary fibrosis and improve lung functions. Due to their immunosuppressive capacity, MSCs significantly decrease the serum levels of pro inflammatory cytokines and chemokines. This leads to decreased attraction of mononuclear/macrophages to the fragile lung, at the same time recruiting more regulatory dendritic cells to the sites of inflammation. They also increase IL-10 and Vascular Endothelial Growth Factor (VEGF), which promotes lung repair.

US FDA has authorized Umbilical cord derived Mesenchymal Stem Cell (MSC) transplant, to prevent life threatening lung inflammation that accompanies severe cases of COVID-19. They have provided authorization for a twenty four patient clinical trial for such patients.

An article related to the use of MSCs in COVID-19 pneumonia, was published by Leng Zikuan, Zhu Ronjia, Hou Wei, et al in the Journal of Aging and Disease, February28, 2020. They studied the effects of MSC transplant on seven COVID-19 patients with pneumonia. A favorable result was reported in all of them.

Use of Convalescent Sera in COVID-19 Patients

Immunity is of two types- active and passive. Active immunity is when the human body mounts an immune reaction in response to an invading microorganism. Passive immunity is when the body is not actively involved in producing immunity. This involves introducing preformed antibodies into the human body through various routes. A classic example of this is the newborn receiving maternal antibodies that protect the newborn till the age of around six months.

Convalescent Sera has been used as early as the twentieth century, to stem the outbreak of viral diseases such as poliomyelitis, measles, mumps and influenza. In the 2009-2010 H1N1 influenza virus pandemic, convalescent sera was used to treat patients with severe H1N1 disease, requiring intensive care. Convalescent serum was also used in the 2013 West African Ebola Virus epidemic. In previous epidemics of Coronaviruses, SARS 1 in 2003 and MERS in 2012, Convalescent Sera was used for patients who were hospitalized.

Recently on April 13, 2020, US FDA issued guidelines to health care providers and investigators on the administration and study of convalescent plasma, collected from individuals who have recovered from COVID-19. COVID-19 convalescent plasma has not yet been approved for use by FDA. It is regulated as an investigational product. Eligibility criteria for the potential patients:

Laboratory confirmed COVID-19.

Severe or immediately life threatening COVID-19, for example:

Informed consent provided by the patient or a health care proxy.

Severe disease is defined as one of the following:

Life threatening disease is defined as one or more of the following:

Shortness of breath (dyspnea)

Respiratory frequency ≥ 30

Blood oxygen saturation ≤ 93%

Ratio of partial pressure of arterial oxygen to fraction of inspired oxygen < 300.

Lung infiltrates > 50% within 24-48 hours.

Respiratory failure.

Septic shock

Multiple organ dysfunction or failure.

So, the research continues, as the pandemic spreads. Scientists, epidemiologists and researchers are working at a fast and furious pace along with the governments of their countries, to expand their knowledge of the disease, its diagnosis and management.

HEALTH DISCLAIMER This blog provides general information and discussions about health and related subjects. The information and other content provided in this blog, or in any linked materials, are not intended and should not be construed as medical advice, nor is the information a substitute for professional medical expertise or treatment. The content is for information purpose only and is not a medical advice. Qualified doctors have gathered information from reputable sources; however Credence Medicure Corporation is not responsible for errors or omissions in reporting or explanations. No individual should use the information, resources and tools contained herein to self diagnose or self treat any medical condition. If you or any other person has a medical concern, you should consult with your health care provider or seek other professional medical treatment. Never disregard professional medical advice or delay in seeking it because of something that have read on this blog or in any linked materials. If you think you may have a medical emergency, call your doctor or emergency services immediately. The opinions and views expressed on this blog and website have no relation to those of any academic, hospital, health practice or other institution. Credence Medicure Corporation gives no assurance or warranty regarding the accuracy, timeliness or applicability of the content.

[outweek30]

A Clinical Trials Primer

Clinical drug trials of any type are not easy to run. Extra care must be taken in community-based trials to guarantee that patients' needs are met, which is, after all, at least half the reason for community trials in the first place. The following is a primer of some of the more pressing ethical and technical issues involved in trials of AIDS drugs.

Controls

Controls are as basic to clinical research as drugs are to medicine. They are usually necessary for collecting accurate data, because they give investigators something with which to compare effects of a given substance. But are these controls always essential when the patients are facing life and death situations? Is it possible to investigate a new drug, without denying many of the test patients access to that drug? Most AIDS activists believe so, and have stepped up debate over several typs of controls.

PLACEBOS: The notorious sugar pill everyone learns about in biology class. Because they are inert, placebos are ideal in many clinical trials: half the subjects are given a drug, the other half receive placebo. These two groups are chosen at random and patients are seldom told which substance they are taking (a process known as "blinding"). But how ethical is it to let one group receive treatment, and live, while others receive a placebo, and die? A 1986 trial of the antiviral AZT gave 20 patients the drug and 20 patients placebos. Six months later, 19 people on placebo had died, while only two on AZT died.

In life or death cases, placebos are immoral, and unnecessary, according to AIDS activists. When CRI and CCC successfully tested aerosolized pentamidine to fight PCP, a pneumonia associated with AIDS, no controls were used. Everyone took the drug, and most people benefitted. There was no need — nor time — to test one group against another.

One other problem with placebos is that patients can find out if they received the drug or the inert substance by having their medication analyzed in a lab. No one knows exactly how many patients manage to find out, but doctors estimated that 10–20 percent in any experiment somehow discover the truth.

ACTIVE CONTROLS: Currently the preferred method among most AIDS activists, including ACT UP, active controls give group A one type of drug, and group B another type. No placebos are used and everyone receives some form of potential therapy. These controls are nearly as effective as placebos in testing the efficacy of a substance. Most active-control experiments today use AZT and ddI (dideoxyinosine), a promising anti-HIV drug.

CROSSOVER CONTROLS: Again, no placebo is used. In this case, group A would switch from, say, three months on AZT to three months on ddI. Information is then obtained by comparing patient reactions to the two drugs.

WAITING LIST CONTROLS: In an experiment testing a popular drug under great demand, doctors can enroll their patients on waiting lists, and compare their data with those who are receiving the drug. Although this is less preferable to active controls, it is often more humane than using placebos, because everyone will receive treatment as soon as possible.

End Points

How long should an experiment last? If there is a clear and proven benefit (or adverse effect) on patients, how much clinical evidence is needed before taking the next step toward approval? Again, the ’86 AZT case is illustrative. Dr. Donald Armstrong of Sloan-Kettering Cancer Center said doctors should look for an "early warning of significance" during trials. "Yes, we have to show efficacy. But did we have to go the full six months to know that 19 patients on placebo would die?" Armstrong asked.

The design of any protocol, then, must include trial "end points." But when can doctors know if an experiment has succeeded or failed? Each case is different, and trial directors must closely watch for these "early warnings," especially if placebos are involved.

Parallel Tracks

Another concept promoted by ACT UP and others — and gaining favor with the NIH and the FDA — is the so-called "parallel track" system. Under this system, drugs that have been proven safe in clinical trials wolud be made available to AIDS, ARC and HIV-positive patients, even while the drugs are still being tested for effectiveness. Thus, parallel track patients could "provide a wealth of information on how a drug worked in the real world," according to a statement released by ACT UP's Treatment and Data Committee.

The system is ideal for many patients who do not fit into any of the rigorous protocols used in clinical trials. Often, people are excluded from trials because they are taking another type of drug. With the parallel track they would not be excluded. This list of advantages is a long one. But using the parallel track would clearly benefit thousands of people while providing AIDS researchers with vital data on promising new drugs.

Avoiding Tragedies

In early July, a man with AIDS died while he was enrolled in an underground study of the antiviral GLQ223, better known as "Compound Q." Federal officials are investigating whether the drug, made from Chinese cucumber root, led to the man's death. Drug safety is essential, and must take precedence over even the most desperate demands of those who would try anything at all.

"We must be very careful. Even though the [compound Q] case is not surprising," said Dr. Armstrong. "PWAs often had to empower themselves every step of the way ... right up to testing drugs themselves.

"But there must be strict guidelines, no coercion and totally informed consent in every protocol," he said.

— Sidebar in OutWeek Magazine No. 5, July 24, 1989, p. 9.

#outweek #issue 5 #lgbt history #hiv aids #act up #parallel track #compound q #drug research #donald armstrong

[marziabbaspour]

Resurge Customer Review | Proven method to get rid of fat?!

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Total Time Needed :30 MinutesTotal Cost:39 USDRequired Tools:- A computer or a mobile phone: As this comes in PDF, you can read it anywhere on your smartphone.Things Needed?- By investing just a few dollars in Resurge and safety gear, you can save thousands of dollars in the long run. How does Resurge work?

As discussed earlier, Resurge works by accelerating metabolic function. As we get older, our metabolisms naturally slow down. This decreases the body’s ability to burn fat effectively which inevitably leads to weight gain. When the fat and calories you eat aren’t burned as energy, the body collects them and stores them as fat. And as you probably already know, this excess fat isn’t easy to get rid of! This is because your metabolism isn’t working as it should. It’s a bad cycle that inevitably causes further weight gain. This is why those 40 and older need a product that gets the metabolism working efficiently. An optimized metabolism encourages weight loss because the body will naturally start to burn fat stores again. It will also be able to burn and use the new fat that you eat as part of your daily diet. Resurge is a trusted supplement that speeds up the metabolism in order to promote weight loss. As you start to shed those excess pounds, you’ll not only see a difference on the scale, but in the mirror as well! Resurge Ingredients

The ingredients that serve as the basis of the Resurge formula are (reported amounts per serving): 1.     L-Arginine (1200mg) L-arginine is a naturally occurring amino acid in the body. In addition, it is believed to contribute to the production of nitric oxide, which in turn is said to relax blood vessels. 2.     L-Lysine (1200mg) Unlike l-arginine, l-lysine is a type of amino acid that the body comes into contact with through food consumption. Interestingly, this ingredient has been found to potentially reduce anxiousness and stress receptors, which together may allow one to sleep better. 3.     L-Theanine (200mg) L-theanine is an amino acid that is supposedly found in teas and certain mushrooms. For a long time now, it has been suggested as a means of improving mental function. To be more specific, it may ease anxiety, mental impairments and stress among others. In fact, when GABA is paired with l-theanine, one can anticipate “a positive synergistic effect on sleep quality and duration.” However, the latter improvement is more apparent together than when the components are taken individually. All in all, this is an amino acid that has many great benefits for sleep. It promotes relaxation and reduces stress levels. It can also assist in the natural production of melatonin which will help you fall asleep easier and sleep better throughout the night. 4.     Ashwagandha (150mg) Ashwagandha is a type of herb/adaptogen that has been long used in ancient medicine, one of them being Ayurveda. Some of its suggested benefits include reduced anxiety, eased feelings of depression, and a boost in cognitive function. 5.     Griffonia Simplicifolia Seed Extract (100mg) Griffonia simplicifolia is a type of plant native to western Africa. It is liked for a chemical called 5-hydroxytryptophan (5-HTP), one that has been commonly used to treat mental health symptoms, weight loss and insomnia. A possible reason why 5-HTP might be helpful is because it creates serotonin, a neurotransmitter that triggers communication with brain cells. In doing so, mood might be regulated, ultimately enhancing sleep.   6.     Melatonin (10mg) Of all the ingredients found in this formula, melatonin appears to be the only one to have a direct impact on sleep. One resource suggests that melatonin supplementation has been found to help people with insomnia fall asleep slightly faster, stressing that the results may vary from person to person. 7.     Magnesium (50mg) Magnesium is a significant mineral seeing that it regulates over 300 enzymatic reactions in the human body. In regard to its effect on sleep, ingesting at least 500mg daily for 8 weeks may improve subjective measures (i.e., Insomnia Severity Index (ISI) questionnaire scores, sleep efficiency, sleep time and sleep onset latency). As for objective impacts, they might include healthy levels of melatonin, serum renin and serum cortisol. 8.     Zinc (15mg) Zinc is an essential trace mineral, as small amounts are trusted to do wonders in the human body. One review disclosed that one of the most “unexpected” roles of zinc is its ability to act as a modulator of sleep. Read the full article

#LearnmoreaboutResurge

[taherehjelodar]

Resurge Customer Review | Proven method to get rid of fat?!

Resurge Review - Is This Pill Right For You? A Resurge review is the perfect place to begin the process of finding a new supplement. This pill is made by John Barban, an American physician and nutritionist who has been working with clients for years. The supplement claims to increase the production of human growth hormone and help the body achieve a healthy circadian rhythm. This helps the body improve its overall functions, including weight loss. While the company does not provide any clinical trials to back up its claims, the ingredients in the pills seem to work. Resurge is available for purchase online. It comes in three bottles, and one will need about three months to get the desired results. The ingredients in Resurge have been extensively tested for safety and efficiency. The company claims that the formula is 100% natural, so it doesn't need any supplements to work. It may not be suitable for those with allergies or those who don't tolerate chemicals in the body. A Resurge review can help you determine if this pill is a good choice for you. One thing to consider before buying Resurge is its reputation. While there are many positive reviews, the product itself has a few flaws. First of all, Resurge is manufactured in the USA in an FDA-approved facility. It follows strict GMP guidelines. Another flaw is the fact that it has no clinical trials. It contains 8 natural ingredients and does not contain any harmful chemicals. It has several advantages but also has a lot of negative side effects. Nevertheless, it's worth checking out before spending money on it. Resurge can be a good choice for people who want to lose fat and maximize the healing power of the body. It can help you burn excess fat while minimizing your risk of disease and aging. There are hundreds of thousands of people seeking to shed the extra fat, but it's a competitive market and many scams and fake products make it easy for desperate people to fall for promises of quick results. Some of these products contain dangerous ingredients or illegal substances to offer instant results. These ingredients can cause long-term damage to the body and may even be harmful to your health. Content Table

Table of contents

- These videos can assist you: - Resurge Customer Review - Part 1 | What is it and who is John Barban? - Resurge Customer Review - Part 2 | How does it work? - Resurge Customer Review - Part 3 | Ingredients - Resurge Customer Review - Part 4 | Pros and Cons + Side effects - Resurge Customer Review - Part 5 | Is it legit or scam? - Resurge Customer Review - Part 6 | Customer's complaints and comments - Resurge Customer Review - Part 7 | Where to buy it + Bonuses- For more Information read this: - Recent Popular Questions: Estimated reading time: 32 minutes These videos can assist you:

Resurge Customer Review - Part 1 | What is it and who is John Barban?

https://youtu.be/XgJxH3_1SXQ 👉 For Get This Extraordinary Product Click Here 👈

Resurge Customer Review - Part 2 | How does it work?

https://youtu.be/rvUPb9Um8eE 👉 For Get This Extraordinary Product Click Here 👈

Resurge Customer Review - Part 3 | Ingredients

https://youtu.be/CwGQkDfuhek 👉 For Get This Extraordinary Product Click Here 👈

Resurge Customer Review - Part 4 | Pros and Cons + Side effects

https://youtu.be/zh1Cmxm6PFQ 👉 For Get This Extraordinary Product Click Here 👈

Resurge Customer Review - Part 5 | Is it legit or scam?

https://youtu.be/Ey2oaAW0pHM 👉 For Get This Extraordinary Product Click Here 👈

Resurge Customer Review - Part 6 | Customer's complaints and comments

https://youtu.be/_oaSb7opIiA 👉 For Get This Extraordinary Product Click Here 👈

Resurge Customer Review - Part 7 | Where to buy it + Bonuses

https://youtu.be/IMp_UoLtLQA 👉 For Get This Extraordinary Product Click Here 👈 For more Information read this: This product is packaged in a gelatin capsule. It contains gelatin, magnesium stearate, and silica. While Resurge is marketed as a vegetarian supplement, the list of ingredients lists gelatin as an ingredient. This substance is a by-product of beef or pork. So, although it is a vegetarian product, the manufacturer of Resurge has not made any changes to ensure its safety. The Resurge team explains the ingredients in the supplement in detail. They claim that there are no side effects associated with the supplement. In addition to its safe and natural composition, Resurge contains several ingredients that help your body to build a strong immune system. Resurge is a supplement that is made by professionals, not amateurs. The manufacturer is committed to quality and safety, and only sells genuine products. You should always purchase the product from its official website to avoid possible problems. Resurge uses natural ingredients that are safe for your body. It does not contain chemicals or other potentially harmful additives. It is manufactured under strict quality standards. Resurge is a supplement that contains natural ingredients. It also does not contain chemicals or harmful ingredients. A Resurge review will help you determine whether this supplement is right for you. If you are interested in weight loss, this supplement is not for you. If you are considering purchasing this product, it is important to read the entire Resurge website. Resurge has many benefits. It is a supplement that can restore normal sleep quality. It works to improve the functioning of leptin and ghrelin hormones in the body. These hormones are responsible for maintaining a normal, stable metabolism. Resurge will help you get a better night's sleep. REM sleep is necessary for a healthy and productive day. By improving your sleeping habits, you will be healthier and happier. Resurge is a vegan supplement that can help you lose weight while enhancing your energy levels. It also targets the root causes of obesity. It does this by increasing metabolic activities while you sleep. When you are asleep, your body is burning fat, which is essential for losing weight. The ingredients in Resurge are natural, and do not contain any GMOs. The formula also contains natural ingredients that are free of GMOs and other artificial ingredients. Recent Popular Questions: How many bottles should I order?According to research, it's advised to take Resurge for at least 90 to 180 days to have the greatest benefits and guarantee you attain and maintain your goal weight. As a result, we highly advise you to take advantage of our three or six bottle savings packages. We can only promise this great rate for today or until our limited quantity runs out, and our present stock is running out quicker than anybody could have predicted. In fact, we promise you'll never be able to get Resurge for less than today's price, which is just another reason why purchasing at least 90-180 days' worth is the sensible choice. Is Resurge safe?Resurge is a completely natural, safe, and effective supplement. Thousands of people love using Resurge every day, and there have been no documented adverse effects. Every Resurge capsule is made in the United States in a state-of-the-art FDA-approved and GMP-certified facility that adheres to the strictest sterile, rigorous, and exact requirements. Resurge is a completely natural, vegetarian, and non-GMO product. If you have a medical issue, you should always speak with your doctor. Will Resurge work for me?In a nutshell, YES! Resurge is the first and only anti-aging nutritional support supplement developed to help women and men increase deep sleep naturally while also reversing metabolic slowness and premature ageing. Resurge contains the correct quantities of 8 scientifically verified nutrients that have been proved to improve deep sleep and metabolic repair. What is the best way to take Resurge?1 hour before bedtime, take Resurge with a glass of water. How will Resurge be shipped to me and how quickly?We'll send your product straight to your home or office using a premium carrier like FedEx or UPS, and you can anticipate it to arrive in 5 to 7 business days if you're in the US or Canada. Orders from outside the United States normally take 8–15 business days to arrive (plus customs clearance time). *Postal delivery delays may be affected by the Covid-19 epidemic. Will I be billed anything else after I order?Certainly not! You may rest confident that this is a one-time payment. This isn't any form of auto-ship programme. There are no additional charges or subscription costs. As much as you despise it, I've always despised it! What if Resurge doesn’t work for me?I'm so convinced that you'll get more deep, life-changing benefits than you've ever had from anything else that I'm not just promising them; I'm going to guarantee them. Resurge comes with a 60-day, no-questions-asked, 100% money-back guarantee, making it a no-brainer for you to get started. If Resurge doesn't turn out to be the finest decision you've ever made, or if you change your mind for any reason, simply email us at [email protected] during the next 60 days, and we'll promptly return your money. My colleagues and I are really accessible. There is no danger to you. It's time to get down to business! Does resurge actually work?Resurge is a natural supplement that aids in falling asleep faster, sleeping more deeply, and waking up feeling rejuvenated. Due to its unique metabolic regeneration matrix, it has been shown to function effectively with those who have chronic insomnia, even after trying other therapies on the market. Does resurge actually work for weight loss?Many of the substances have been shown to aid in sleep, relaxation, and other health benefits. However, there isn't enough evidence to suggest that Resurge can increase fat burning while you sleep or lead to considerable weight reduction. What happens when you stop taking resurge?If this occurs, the person may experience nausea, dizziness, and headaches. Once the dose is returned to normal or the customer stops taking the tablets for a short period of time, the negative effects should disappear. Side effects that are severe or persistent should be reported to a doctor. What does resurge do to your body?As you go off to sleep, the Resurge supplement relaxes your brain and body. Magnesium also includes GABA receptors, which help you sleep by reducing brain activity. An amino acid that can help to calm the body and reduce tension and anxiety in the brain. Who is John Barban?John Barban, a fat reduction specialist and licenced nutrition and wellness expert, is the creator of Java Burn and its coffee supplementation method. He is a three-time best-selling book and industry-renowned natural supplement formulator. What is Resurge and Who is John Barban?Resurge Review: Weight loss is much more than just eating healthy and exercising, as stress, poor habits, and certain medical conditions and medications can significantly impact results. However, the one factor that often goes missed is sleep quality. As per existing research, there is a positive correlation between sleep and healthy body weight. In other words, as individuals attain enhanced sleep quality, the more likely they are to maintain their weight. Resurge is a deep sleep and high support formula that aims to optimize one’s sleep schedule. As a result, individuals can expect to wake up feeling “leaner, healthier, younger and way more energized” than their older selves. Resurge pills are perfect for those who are deprived of restorative sleep, known for healing the body, repairing tissues and cells, and ensuring proper functioning of the body. Resurge Supplement are helpful, especially in these days when technology is stripping people of a healthy lifestyle and starving their sleep. The man behind Resurge is John Barban, the world’s leading expert in metabolism and weight loss. He is a popular fitness instructor and coach who carved a niche for himself by helping both men and women to find innovative ways to lose stubborn weight. Barban has acquired his degree in human biology and nutrition, which has proven to be a great strength in his line of work. Previously, he came up with several weight loss solutions including Venus Factor, which became very popular among women. However, later on, John Barban introduced his new fat burn supplement in the name of Resurge and announced it to be the best way to lose weight and improve one’s overall well-being. He gives you instructions, techniques, and some easy ways to get deep sleep and lose weight quickly. John Barban is a famous sleep creator too. He transformed millions of people around the world through his Resurge supplement. John Barban has shared his struggle with visceral fat, low metabolic activity, and depression, and has credited Resurge ingredients (taken in the right proportion) for curing his woes.

Total Time Needed :30 MinutesTotal Cost:39 USDRequired Tools:- A computer or a mobile phone: As this comes in PDF, you can read it anywhere on your smartphone.Things Needed?- By investing just a few dollars in Resurge and safety gear, you can save thousands of dollars in the long run. How does Resurge work?

As discussed earlier, Resurge works by accelerating metabolic function. As we get older, our metabolisms naturally slow down. This decreases the body’s ability to burn fat effectively which inevitably leads to weight gain. When the fat and calories you eat aren’t burned as energy, the body collects them and stores them as fat. And as you probably already know, this excess fat isn’t easy to get rid of! This is because your metabolism isn’t working as it should. It’s a bad cycle that inevitably causes further weight gain. This is why those 40 and older need a product that gets the metabolism working efficiently. An optimized metabolism encourages weight loss because the body will naturally start to burn fat stores again. It will also be able to burn and use the new fat that you eat as part of your daily diet. Resurge is a trusted supplement that speeds up the metabolism in order to promote weight loss. As you start to shed those excess pounds, you’ll not only see a difference on the scale, but in the mirror as well! Resurge Ingredients

The ingredients that serve as the basis of the Resurge formula are (reported amounts per serving): 1.     L-Arginine (1200mg) L-arginine is a naturally occurring amino acid in the body. In addition, it is believed to contribute to the production of nitric oxide, which in turn is said to relax blood vessels. 2.     L-Lysine (1200mg) Unlike l-arginine, l-lysine is a type of amino acid that the body comes into contact with through food consumption. Interestingly, this ingredient has been found to potentially reduce anxiousness and stress receptors, which together may allow one to sleep better. 3.     L-Theanine (200mg) L-theanine is an amino acid that is supposedly found in teas and certain mushrooms. For a long time now, it has been suggested as a means of improving mental function. To be more specific, it may ease anxiety, mental impairments and stress among others. In fact, when GABA is paired with l-theanine, one can anticipate “a positive synergistic effect on sleep quality and duration.” However, the latter improvement is more apparent together than when the components are taken individually. All in all, this is an amino acid that has many great benefits for sleep. It promotes relaxation and reduces stress levels. It can also assist in the natural production of melatonin which will help you fall asleep easier and sleep better throughout the night. 4.     Ashwagandha (150mg) Ashwagandha is a type of herb/adaptogen that has been long used in ancient medicine, one of them being Ayurveda. Some of its suggested benefits include reduced anxiety, eased feelings of depression, and a boost in cognitive function. 5.     Griffonia Simplicifolia Seed Extract (100mg) Griffonia simplicifolia is a type of plant native to western Africa. It is liked for a chemical called 5-hydroxytryptophan (5-HTP), one that has been commonly used to treat mental health symptoms, weight loss and insomnia. A possible reason why 5-HTP might be helpful is because it creates serotonin, a neurotransmitter that triggers communication with brain cells. In doing so, mood might be regulated, ultimately enhancing sleep.   6.     Melatonin (10mg) Of all the ingredients found in this formula, melatonin appears to be the only one to have a direct impact on sleep. One resource suggests that melatonin supplementation has been found to help people with insomnia fall asleep slightly faster, stressing that the results may vary from person to person. 7.     Magnesium (50mg) Magnesium is a significant mineral seeing that it regulates over 300 enzymatic reactions in the human body. In regard to its effect on sleep, ingesting at least 500mg daily for 8 weeks may improve subjective measures (i.e., Insomnia Severity Index (ISI) questionnaire scores, sleep efficiency, sleep time and sleep onset latency). As for objective impacts, they might include healthy levels of melatonin, serum renin and serum cortisol. 8.     Zinc (15mg) Zinc is an essential trace mineral, as small amounts are trusted to do wonders in the human body. One review disclosed that one of the most “unexpected” roles of zinc is its ability to act as a modulator of sleep. Read the full article

#LearnmoreaboutResurge

[insidealternatemedicine]

Psilocybin Research

In the year 2000 John hopkins University received regulatory approval to resume researching psychedelics in healthy patients,

In 2020, Oregon became the first state to legalize psilocybin, a natural hallucinogen found in psychedelic “magic” mushrooms. Much like the historic legalization of cannabis for medicinal purposes in California in 1996, this may be the start of a legalization trend across US jurisdictions. Similar to medical cannabis, you can pinpoint promising research results for psilocybin therapy treatments as the reason behind this new trend.

Although it’s yet to receive FDA approval, research has shown that psilocybin may help treat a variety of psychiatric and behavioral disorders.

https://getheally.com/patients/news/magic-mushrooms-the-potential-medical-benefits-of-psilocybin

Center Highlights and research timeline

"1. 2000(Research):Regulatory approval to resume psychedelics research

A group of Johns Hopkins researchers was the first to obtain regulatory approval in the United States to resume research with psychedelics in healthy volunteers who had no previous experience with psychedelics.

2. 2006(Milestone):Milestone study launching the revival of psilocybin research,

Let the study Begin!

The publication "Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance" on the safety and enduring positive effects of a single dose of psilocybin is widely considered the landmark study that sparked a renewal of psychedelic research world-wide.

See More Academic Papers

3. 2008(Document):Guidelines for safety

The Center’s team emphasizes safety as a cornerstone of psychedelics research. These recommended techniques in this publication, "Human hallucinogen research: guidelines for safety," have been adopted by others in the field.

Read the Paper

Results.

4. 2014(Document):'Magic mushrooms' help longtime smokers quit

Johns Hopkins researchers report that a small number of longtime smokers who had failed many attempts to drop the habit did so after a carefully controlled and monitored use of psilocybin, the active hallucinogenic agent in so-called "magic mushrooms,” in the context of a cognitive behavioral therapy treatment program.

80% still non smoking after 6 months

Read the News Release

5. 2016(Document): Psilocybin eases existential anxiety in people with life threatening cancer

In a small double-blind study, Johns Hopkins researchers report that a substantial majority of people suffering cancer-related anxiety or depression found considerable relief for up to six months from a single large dose of psilocybin — the active compound in hallucinogenic “magic mushrooms.”

Read the News Release

6. 2018(Research):Reclassification recommendation for psilocybin

In an evaluation of the safety and abuse research on the drug in hallucinogenic mushrooms, Johns Hopkins researchers suggest that if it clears phase III clinical trials, psilocybin should be re-categorized from a schedule I drug—one with no known medical potential—to a schedule IV drug such as prescription sleep aids, but with tighter control.

Read the News Release

7. 2019(Document)

Psychedelic use may lead to treatments for alcohol abuse

Online survey of over 300 people with Alcohol Use Disorder reported reducing or abstaining alcohol use after taking a psychedelic drug such as psilocybin, LSD or DMT. This study adds to growing evidence for supporting further investigation of psychedelic-assisted treatment for alcoholism or substance abuse.

Read the Paper

Johns Hopkins launches center for psychedelic research

A group of private donors has given $17 million to start the Center for Psychedelic and Consciousness Research at Johns Hopkins Medicine, making it what’s believed to be the first such research center in the U.S., and the largest research center of its kind in the world. In the absence of federal funding for such therapeutic research in people, the new center will rely on the gifts announced today to advance the emerging field of psychedelics for therapies and wellness.

Read the News Release

8. 2020(Document):Psychedelic Drug Psilocybin Tamps Down Brain’s Ego Center

The brain scans after psilocybin use showed that the claustrum was less active, meaning the area of the brain believed responsible for setting attention and switching tasks is turned down when on the drug. The researchers say that this ties in with what people report as typical effects of psychedelic drugs, including feelings of being connected to everything and reduced senses of self or ego." Hopkins Research Institute

Roland Griffiths, Ph.D., director, Center for Psychedelic and Consciousness Research at Johns ... [+]

(PHOTO COURTESY OF CENTER FOR PSYCHEDELIC AND CONSCIOUSNESS RESEARCH)

Griffiths will head up the new Center for Psychedelic and Consciousness Research at Johns Hopkins Medicine. The first of its kind in the U.S. and the largest research center of its kind in the world, the center is being funded initially by a $17 million donation from a group of private donors ( Steven & Alexandra Cohen Foundation and four philanthropists: Tim Ferriss (author and technology investor), Matt Mullenweg (co-founder of WordPress), Blake Mycoskie (founder of TOMS, a shoe and accessory brand) and Craig Nerenberg (investor).)to advance the emerging field of psychedelics for therapies and wellness. The center will house a team of six faculty neuroscientists, experimental psychologists and clinicians with expertise in psychedelic science, as well as five postdoctoral scientists. Graduate and medical students who want to work in psychedelic science, but have had few avenues to study in such a field, will be trained at the center.

“We have to take braver and bolder steps if we want to help those suffering from chronic illness, addiction and mental health challenges,”

Alex Cohen, president of the Steven & Alexandra Cohen Foundation and a center-funder, said in a statement.

“By investing in the Johns Hopkins center, we are investing in the hope that researchers will keep proving the benefits of psychedelics — and people will have new ways to heal.”

People who have been treated with psilocybin often rate their encounters with psilocybin as among

"the most personally meaningful experiences of their entire lives,”

Griffiths said.

"It is fundamentally different than any other psychoactive drug. Because these experiences occur in most people, studies often look very similar to naturally-occurring experiences, and they appear to be biologically normal. That is, we seem to be wired to have such experiences."

“Some would hold that we were evolutionarily selected for such experiences because it results in some survival advantage."

Griffiths says that some people interpret the experience as an encounter with ultimate reality or with God.

And the drugs seem to offer neuroplasticity, or the ability of the brain to change, he said, allowing people to get out of the habitual ruts they have put themselves in as new neuropathways are formed. Griffiths said people claim that “it feels like a home-coming or an epiphany that allows them to rewrite the narrative of their lives.”

And other notable educational institutions are studying the possibilities of therapy with psychedelics, he said, including New York University (NYU), Yale University (YU), University of Alabama at Birmingham (UAB), University of California, Los Angeles (UCLA), University of California, San Fransisco (UCSF) and University of Wisconsin-Madison (UW-Madison). For now, the center will focus on how psychedelics affect behavior, brain function, learning and memory, the brain’s biology and mood, Johns Hopkins announced last week.

“Studies of psilocybin in patients will determine its effectiveness as a new therapy for opioid addiction, Alzheimer's disease, post-traumatic stress disorder (PTSD), post-treatment Lyme disease syndrome (formerly known as chronic Lyme disease), anorexia nervosa and alcohol use in people with major depression. The researchers hope to create precision medicine treatments tailored to individual patients’ specific needs.”

Forbes

More In depth Information about the studies

Safety

In 2011, Studerus et al8 compiled data from 8 different studies involving psilocybin administration from 1999 to 2008. This pooled analysis consisted of 110 healthy human subjects who received 1 to 4 different oral doses of psilocybin for a total of 227 psilocybin administrations. The doses used throughout the studies ranged from 45 mcg/kg to 315 mcg/kg. All subjects underwent extensive screening prior to entering the studies and were excluded if they had any active Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis or emotional liability.8,9 All of the studies used the Altered States of Consciousness Rating Scale, which is a visual self-rating scale. Short- and long-term safety was evaluated, and there was no indication of increased drug abuse, persisting perception disorders, prolonged psychosis, or other long-term deficits in functioning. The number of adverse reactions from psilocybin was few in number, resolved quickly, and was mostly associated with the highest doses of psilocybin. The subjects were followed for 8 to 16 months post psilocybin administration and exhibited no long-term negative side effects.8 The safety demonstrated in this study opened the door for more research on psilocybin. It should be noted, however, that the administration of psilocybin in these studies followed strict protocols and therefore may lack external validity to the general population.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007659/

There has been some concern that use of psychedelic agents in a mental health population could exacerbate the underlying disease or cause suicidal behavior despite little clinical data showing significant safety issues or development of addiction with the administration of hallucinogens. Johansen and Krebs10 set out to examine this claim and published a population study detailing their findings. This population study of 135 095 random adults in the United States included 19 299 psychedelic users (which included LSD, mescaline, and psilocybin). No significant association was found between lifetime use of psychedelics and increased mental health treatment or suicidal thoughts, plans, or attempts.10

Additionally, a review of psilocybin use in the Netherlands demonstrated similar findings. Per the authors' conclusions, dependence potential was low, acute toxicity was moderate (few mild or severe adverse reactions), chronic toxicity was low, and public health risks were negligible.11 In contrast to this conclusion, 1 article describes severe adverse effects of high doses (approximately 420 mcg/kg), including a high incidence of significant fear and transient ideas of reference/paranoia (31% and 17%, respectively) in healthy volunteers.12 Per the Netherlands article, the average lethal dose (LD50) in rats was 280 000 mcg/kg, equating to approximately 17 kg of mushrooms ingested. The article details only 4 case reports directly attributing death to psilocybin use over a 41-year period. Many other fatal case reports mentioned in the article were in combination with other drugs of abuse (alcohol, heroin, and cannabis).11 It appears that low-to-moderate doses of psilocybin are fairly well tolerated although it should be noted that the number of articles describing psilocybin use is small, and there have been fatalities reported. However, compared to other common drugs of abuse, such as heroin, the death risk appears to be much smaller.

Suicidality and depressed Mood

Hendricks et al13 examined the relationship of lifetime psilocybin use and psychological distress in the past month. They also collected past-year suicidal thinking, suicidal planning, and suicide attempts associated with psilocybin use in an adult population in the United States. Data used was from the National Survey on Drug Use and Health (2008-2012)14 in which 191 831 participants were divided into 1 of 4 groups: psilocybin use only (n = 7550), psilocybin and other psychedelics (n = 12 724), other nonpsilocybin psychedelics only (n = 6963), or no psychedelic use in their lifetime (n = 164 595). The odds of all of the outcomes were reduced in the psilocybin-only group compared to the no psychedelic use group. Past-year suicidal thinking and planning were lower in the psilocybin group compared to the psilocybin and other psychedelics group. Finally, the odds of past-month psychological distress were lower in the psilocybin group relative to the other psychedelics-only group. Based on this data, the psilocybin group appeared to fare better than any other group. This further supports the idea that psilocybin may play a role in reducing suicidality and improving mood although these patients did not necessarily have a diagnosis of major depressive disorder. It also highlights the potential safety of the substance in such a large population.13

Griffiths and colleagues12,15 published articles in 2006 and 2008 examining the psychological effects of psilocybin in healthy volunteers. Hallucinogen-naïve adults were given oral psilocybin or methylphenidate in 2 or 3 sessions. They were told that they would receive a moderate or high dose of psilocybin during at least 1 of the sessions. At both 2 months postdrug sessions and 14 months follow-up, the patients had significantly increased ratings of positive attitudes, mood, social effects, and behavior with the psilocybin sessions compared to the methylphenidate sessions. The authors felt that the biggest finding of their study was that a large percentage of the patients rated their psilocybin experience as one of the most meaningful experiences of their lives. As patient buy-in to therapy is important with mental health, this level of satisfaction with treatment may actually increase efficacy. Also, the 14-month follow-up showed no evidence of adverse effects due to psilocybin exposure based on patient interview. Psilocybin was administered in a controlled environment in this study; thus, external validity may be decreased compared to the general mental health population.15

Anxiety

Some of the first clinical research on psilocybin studied its use in treating anxiety symptoms in patients with cancer. Grob et al16 completed a double-blind, placebo-controlled study to examine the safety and efficacy of psilocybin in 12 patients for the treatment of psychological distress associated with the existential crisis of terminal disease. Inclusion criteria were a diagnosis of acute stress disorder, generalized anxiety disorder, anxiety disorder due to cancer, or adjustment disorder with anxiety per the DSM-IV criteria along with a diagnosis of advanced-stage cancer.9,16 Patients were randomized to receive either active psilocybin (200 mcg/kg) or niacin 250 mg, both in oral capsule formulation. Niacin was chosen as the control because researchers thought it would provide the warm flushing effect, a common adverse effect of psilocybin, without altering the psychological state. Patients served as their own control and received 2 treatment sessions (1 with psilocybin and 1 with niacin) spaced several weeks apart. Patients were with staff for the entire 6-hour session, and vital signs were monitored. Several rating scales were used the day before, day of, and day after each session along with 2 weeks, monthly, and 6 months postsession. Anxiety significantly decreased as measured by the State-Trait Anxiety Inventory at 1 and 3 months posttreatment in the psilocybin group compared to niacin. Mood improved for 2 weeks after treatment and reached statistical significance on the Beck Depression Inventory at the 6-month point with the same comparison. In terms of safety data, the psilocybin group did have a modest increase in heart rate and blood pressure at 2 hours after ingestion. Holter monitoring did not show any increased risk of cardiac arrhythmias in the psilocybin group compared to the niacin group.16 This small study of a relatively low dose of psilocybin supports further research on whether psilocybin could be used as a medication for the management of anxiety disorders.

Tobacco cessation

Some of the first clinical research on psilocybin studied its use in treating anxiety symptoms in patients with cancer. Grob et al16 completed a double-blind, placebo-controlled study to examine the safety and efficacy of psilocybin in 12 patients for the treatment of psychological distress associated with the existential crisis of terminal disease. Inclusion criteria were a diagnosis of acute stress disorder, generalized anxiety disorder, anxiety disorder due to cancer, or adjustment disorder with anxiety per the DSM-IV criteria along with a diagnosis of advanced-stage cancer.9,16 Patients were randomized to receive either active psilocybin (200 mcg/kg) or niacin 250 mg, both in oral capsule formulation. Niacin was chosen as the control because researchers thought it would provide the warm flushing effect, a common adverse effect of psilocybin, without altering the psychological state. Patients served as their own control and received 2 treatment sessions (1 with psilocybin and 1 with niacin) spaced several weeks apart. Patients were with staff for the entire 6-hour session, and vital signs were monitored. Several rating scales were used the day before, day of, and day after each session along with 2 weeks, monthly, and 6 months postsession. Anxiety significantly decreased as measured by the State-Trait Anxiety Inventory at 1 and 3 months posttreatment in the psilocybin group compared to niacin. Mood improved for 2 weeks after treatment and reached statistical significance on the Beck Depression Inventory at the 6-month point with the same comparison. In terms of safety data, the psilocybin group did have a modest increase in heart rate and blood pressure at 2 hours after ingestion. Holter monitoring did not show any increased risk of cardiac arrhythmias in the psilocybin group compared to the niacin group.16 This small study of a relatively low dose of psilocybin supports further research on whether psilocybin could be used as a medication for the management of anxiety disorders.

[your-dietician]

Long-Term CRYSVITA® ▼ (burosumab) Treatment Reduces the Burden of Disease in Adults With X-Linked Hypophosphataemia (XLH), a Rare Genetic Metabolic Bone Disease

New Post has been published on https://depression-md.com/long-term-crysvita-%e2%96%bc-burosumab-treatment-reduces-the-burden-of-disease-in-adults-with-x-linked-hypophosphataemia-xlh-a-rare-genetic-metabolic-bone-disease/

Long-Term CRYSVITA® ▼ (burosumab) Treatment Reduces the Burden of Disease in Adults With X-Linked Hypophosphataemia (XLH), a Rare Genetic Metabolic Bone Disease

TOKYO–(BUSINESS WIRE)–Kyowa Kirin Co., Ltd. (TSE:4151, Kyowa Kirin) today announced the publication of new data highlighting the sustained benefits of treatment with CRYSVITA® (burosumab) in adults with X-linked hypophosphataemia (XLH), a rare genetic metabolic bone disease. The data show that adults with XLH experience substantial pain, stiffness, fatigue and impairment in physical and ambulatory function. Treatment with CRYSVITA was associated with a significant improvement from baseline after 96 weeks.1

The data are from a randomised, double-blind, placebo-controlled, phase 3 study with an open-label extension to assess the efficacy and safety of CRYSVITA in adults with XLH.2 The study met its primary endpoint, showing a statistically significant effect in increasing serum phosphorus concentrations at 24 weeks, compared to placebo.3 After 24 weeks, all patients were switched to CRYSVITA treatment and data was collected on metabolic and biochemical markers, patient reported outcomes (PROs) and measures of mobility up to 96 weeks. This new publication focuses on the results from the PRO analysis and mobility scores.1

At week 96, the study showed statistically significant improvements in PROs, including the Western Ontario and the McMaster Universities Osteoarthritis Index (WOMAC), Brief Pain Inventory–Short Form (BPI-SF) and Brief Fatigue Inventory (BFI), compared to baseline.1 Statistically significant improvements in ambulatory function, measured by the 6-minute walk test (6MWT), were also seen at 96 weeks compared to baseline.1 Data previously published at 48 weeks also showed improvements in some PROs, including stiffness and pain, as well as fracture healing.3

Lead author Pr Karine Briot, Hôpital Cochin, Paris, France said: “The study highlights the many physical challenges faced by adult patients with XLH, including pain, stiffness, fatigue and difficulty walking or physical function. Burosumab treatment has previously been shown to improve phosphate homeostasis in adult XLH patients, compared to placebo. This new analysis suggests that, despite the long-term complications and physical impairment associated with XLH in adults, treatment with burosumab can also improve the physical function and quality of life of adults with XLH over the longer term.”

Tomohiro Sudo, Executive Officer, Head of Global Product Strategy Department of Kyowa Kirin, said: “Kyowa Kirin is committed to improving the lives of people with XLH and their families. One of our areas of focus is to generate new data that improve our understanding of how best to manage and treat XLH. These important new data highlight the many physical challenges that people living with XLH face every day, how their needs could be better met and how Kyowa Kirin is delivering on its purpose, to make people smile.”

The data were published today in the BMJ journal RMD Open, Rheumatic and Musculoskeletal Diseases.1 CRYSVITA is licensed in Europe for the treatment of XLH in children and adolescents aged 1 to 17 years with radiographic evidence of bone disease, and in adults.4

▼This medicinal product is subject to additional monitoring.

About X-linked hypophosphataemia

X-linked hypophosphataemia (XLH) is a rare, genetic disease that causes abnormalities in the bones, muscles, and joints.5,6 XLH is not life-threatening, but its burden is life-long and progressive, and it may reduce a person’s quality of life.7

People with XLH have a genetic defect on the X-chromosome, which causes an excessive loss of phosphate through the urine and poor absorption from the gut due to excess of a hormone known as fibroblast growth factor-23 (FGF23), resulting in chronically low levels of phosphate in the blood.4,8 Phosphate is a key mineral needed for maintaining the body’s energy levels, muscle function, and the formation of healthy bones and teeth.9,10 While there is no cure for XLH, therapies aimed at helping to restore and maintain phosphate to normal levels within the body may help to improve the progression of disease symptoms.2

XLH is the most common form of hereditary rickets.11 It can sometimes appear in individuals with no family history of the disease but is usually passed down from a parent who carries the defective gene.12

About CRYSVITA® (burosumab)

CRYSVITA (burosumab) was created and developed by Kyowa Kirin and is a recombinant fully human monoclonal IgG1 antibody against the phosphaturic hormone fibroblast growth factor 23 (FGF23). FGF23 is a hormone that reduces serum levels of phosphate by regulating phosphate excretion and active vitamin D production by the kidney. Phosphate wasting and resulting hypophosphataemia in X-linked hypophosphataemia (XLH) is caused by excess FGF23. CRYSVITA is designed to bind to, and thereby inhibit, the biological activity of FGF23. By blocking excess FGF23 in patients, CRYSVITA is intended to increase phosphate reabsorption from the kidney and increase the production of active vitamin D, which enhances intestinal absorption of phosphate and calcium.

CRYSVITA has been available for clinical use since 2018. The first approval came from the European Commission, that granted a conditional marketing authorisation for CRYSVITA for the treatment of XLH with radiographic evidence of bone disease in children one year of age and older and adolescents with growing skeletons. In 2020, this authorisation was subsequently expanded to include older adolescents and adults.2

CRYSVITA is approved by the US Food and Drug Administration (FDA) for patients with XLH aged 6 months and older and by Health Canada for patients with XLH aged one year and older.13,14

In 2019, CRYSVITA received approval from Japan’s Ministry of Health, Labour and Welfare for the treatment of FGF23-related hypophosphataemic rickets and osteomalacia. In 2020, CRYSVITA was reimbursed by National Health Insurance (NHI) in Japan as a self-injection presentation for the treatment of FGF23-related hypophosphataemic rickets and osteomalacia.

In January 2020, Swissmedic approved CRYSVITA for the treatment of adults, adolescents and children (one year of age and older) with XLH.15

In June 2020, the U.S. Food and Drug Administration (FDA) approved CRYSVITA for patients aged two and older with tumour-induced osteomalacia (TIO), a rare disease that is characterised by the development of tumours that cause weakened and softened bones.16

Kyowa Kirin and Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE: Ultragenyx) have been collaborating in the development and commercialisation of CRYSVITA globally, based on the collaboration and licence agreement between Kyowa Kirin and Ultragenyx.

About Kyowa Kirin

Kyowa Kirin strives to create and deliver novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company with a more than 70-year heritage, the company applies cutting-edge science including an expertise in antibody research and engineering, to address the needs of patients and society across multiple therapeutic areas including Nephrology, Oncology, Immunology/Allergy and Neurology. Across our four regions – Japan, Asia Pacific, North America and EMEA/International – we focus on our purpose, to make people smile, and are united by our shared values of commitment to life, teamwork/Wa, innovation, and integrity. You can learn more about the business of Kyowa Kirin at: https://www.kyowakirin.com/

Kyowa Kirin International

http://www.international.kyowa-kirin.com / www.kyowakirin.com

Galabank Business Park

Galashiels, TD1 1QH

United Kingdom

References

1 Briot K, Portale AA, Brandi ML, et al. RMD Open 2021;7:e001714. doi: 10.1136/rmdopen-2021-001714.

2 Insogna KL, Rauch F, Kamenický P, et al. Burosumab improved histomorphometric measures of osteomalacia in adults with X-linked hypophosphatemia: a Phase 3, single-arm, international trial. J Bone Miner Res. 2019;34:2183-2191.

3 Portale AA, Carpenter TO, Brandi ML, et al. Calcif Tissue Int 2019;105:271–84.

4 European Medicines Agency. CRYSVITA EPAR product information. Summary of Product Characteristics. Available at: Crysvita, INN-burosumab; (europa.eu). Last updated: June 2021. Last accessed: July 2021.

5 Linglart A, Biosse-Duplan M, Briot K, et al. Therapeutic management of hypophosphatemic rickets from infancy to adulthood. Endocr Connect. 2014;3:R13-30.

6 Haffner D, Emma F, Eastwood DM, et al. Consensus Statement. Evidence-based guideline. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphatemia. Nat Rev Nephrol. 2019;15;435-455.

7 Skrinar A, Dvorak-Ewell M, Evins A, et al. The lifelong impact of X-linked hypophosphatemia: Results from a burden of disease survey. J Endocr Soc. 2019;3:1321-1334.

8 Beck-Nielsen SS, Mughal Z, Haffner D, et al. FGF23 and its role in X-linked hypophosphatemia-related morbidity. Orphanet J Rare Dis. 2019;14:58.

9 Pesta D, Tsirigotis DN, Befroy DE, et al. Hypophosphatemia promotes lower rates of muscle ATP synthesis. The FAESB Journal. 2016;39:3378-3387.

10 Unnanuntana A, Rebolledo BJ, Khair MM, et al. Diseases affecting bone quality: beyond osteoporosis. Clin Orthop Relat Res. 2011;469:2194-2206.

11 Carpenter TO, Imel EA, Holm IA, et al. A clinician’s guide to X-linked hypophosphatemia. J Bone Miner Res. 2011;26:1381-8.

12 National Center for Advancing Translational Sciences. X-linked hypophosphatemia. Available at: https://rarediseases.info.nih.gov/diseases/12943/x-linked-hypophosphatemia. Last updated: February 2018. Last accessed: July 2021.

13 Health Canada. Regulatory Decision Summary – CRYSVITA. Available at: https://hpr-rps.hres.ca/reg-content/regulatory-decision-summary-detail.php?linkID=RDS00463. Last updated: April 2020. Last accessed: April 2021.

14 Available at : https://www.kyowakirin.com/media_center/news_releases/2019/e20190930_01.html. Last accessed: July 2021

15 Swissmedic. Crysvita, injektionslösung (burosumabum). Available at: https://www.swissmedic.ch/swissmedic/en/home/humanarzneimittel/authorisations/new-medicines/vrysvita-injektionsloesung_burosumabum.html. Last updated: January 2020. Last accessed: July 2021.

16 FDA. Available at: FDA Approves First Therapy for Rare Disease that Causes Low Phosphate Blood Levels, Bone Softening | FDA. Last accessed: July 2021

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Following are some of the landmarks of the new drug testing order:

September 1986: Spurred by striking differences in mortality between the placebo group (19 deaths) and the AZT group (two deaths), Burroughs-Wellcome stops its Phase II trial of AZT and distributes the drug widely under the first "treatment IND (investigational new drug" program.

March 1987: FDA approves AZT in record time.

May 1987: FDA publishes new guidelines codifying the treatment IND program. Under treatment IND, drugs may be distributed widely before final approval, if FDA approves.

October 1987: FDA advisory committee refuses to recommend approval for DHPG (ganciclovir), a drug that prevents blindness in people with AIDS, even though there is no alternative treatment. The reason? No placebo-controlled clinical trials were conducted.

July 1988: Vice President Bush meets with FDA Commissioner Frank Young, MD, and requests FDA reforms to speed up testing and widen availability of new drugs for cancer and AIDS. This is the impetus behind the so-called "Bush Initiative" (see October 1988) and the Lasagna Committee (see 1989).

August 1988: Trimetrexate, an anti-PCP drug, is the first to get treatment IND status. FDA interprets it narrowly and only 89 people get the drug. Lambda Legal Defense & Education Fund threatens a lawsuit. FDA relents and allows wider distribution.

October 1988: October 11: 1,500 AIDS activists from around the country besiege the FDA in Rockville, MD. It's the first time a federal agency has ever been shut down by the group the agency exists to protect. October 21: The so-called "Bush Initiative" is released. Guidelines provide for skipping the third phase of drug tests if the second phase is promising. Guidelines won't save lives, only drugs will. Hoffman-LaRoche is rumored to be planning on using the new guidelines in its trials of antiviral ddC (dideoxycytidine).

December 1988: FDA gives ganciclovir (DHPG) Treatment IND status. To qualify, patients must be ineligible for a controlled study in which they would have a 50 percent chance of getting no treatment at all. Universal outcry from AIDS activists.

January 1989: First hearings of the Lasagna Committee (so named after its chairman, Dr. Louis Lasagna), in Bethesda MD, a federal panel to recommend reforms to streamline AIDS and cancer drug trials. National Cancer Institute director Dr. Sam Broder (discoverer of anti-HIV activity of AZT, ddC, ddI and other new drugs) publicly lambasts the FDA for rigid micromangement and delays.

February 1989: Activists boo FDA Anti-Viral Drug Director Dr. Ellen Cooper at second hearing of Lasagna Committee, Cooper tries to justity the agency's refusal to approve DHPG, ACT UP representatives meet with Dr. Anthony Fauci, who oversees federal AIDS trials. Fauci agrees to publicly call for DHPG's'release.

March 1989: FDA reverses policy and allows resumed access to DHPG for people who don't qualify for clinical trials.

May 1989: ACT UP testifies at the Lasagna Committee. The bureaucrats begin to listen.

June 1989: Because the government lacks a comprehensive AIDS research strategy, the AIDS community must come up with one.

June 6: After taking over the opening ceremonies of the Fifth International Conference on AIDS in Montreal, ACT UP presents its National AIDS Treatment Research Agenda.

June 15: FDA approves aerosolized pentamidine for prophylacxis (prevention) of PCP. It's the first time a drug has been approved based on community-based research.

June 21: ACT UP meets with NIAID's Dr. Anthony Fauci in Bethesda. He endorses a new program allowing new anti-AIDS drugs to be released on a "parallel track" trial if the patient is unable to enter the controlled trial (e.g., someone who couldn't take AZT and hence couldn't enter a trial comparing AZT with ddI could get into a parallel trial of ddI).

June 22: ACT UP meets with FDA's Dr. Ellen Cooper. She supports the idea of parallel trials. But she shows herself unwilling to support wider distribution of Foscarnet, an antiviral drug needed to prevent cytomegalovirus (CMV) retinitis in people whose CMV has developed resistance to DHPG, She says (in another context but with a chilling double meaning) that "there are advantages to blinding."

June 24: ACT UP meets with Bristol-Myers in New York, manufacturers of ddI. It's the first time a pharmaceutical company ever met with members of an affected community before conducting broad clinical trials. Bristol-Myers is nervous and won't commit itself to distributing ddI on a parallel track.

June 24: In San Francisco Dr. Fauci publicly endorses the idea of "parallel track" distribution of new AIDS drugs at an HIV conference sponsored by Project Inform.

June 26: FDA approves DHPG for treatment of CMV retinitis. It's the first time a drug has been approved without undergoing controlled clinical trials. Also, FDA grants Treatment IND status to erythropoietin (EPO) for treatment of AZT-related anemia. (As many as half those on AZT get anemia, depleted red blood cells, and require frequent transfusions. EPO raises their red blood count and reduces the frequency of transfusions.)

People with AIDS, HIV and their advocates have fought tirelessly for these victories, The government, as embodied in FDA bureaucrats and NIH scientists, has begun to respond. Yet pharmaceutical companies are reluctant to distribute new drugs widely enough, the insurance companies are refusing to pay for them. By the end of 1989, AIDS advocates must force the pharmaceutical and insurance companies to fall in line with the new epoch of humane drug testing for life-threatening diseases.

June 26: The Centers for Disease Control (CDC) in Atlanta reports that, by May 31, 97,193 Americans have been reported as having AIDS. 56,468 have died. The US Public Health Service (PHS) estimates between 945,000 and 1,400,000 Americans are HIV-infected. By 1992, according to the PHS, 365,000 Americans will have been reported to have AIDS, and 263,000 will have died.

The government anticipates that 206,532 people now alive will die from AIDS by 1992, Those deaths are preventable. Treatments which can prevent many of them exist. They must be distributed to people who need them. Treatments for conditions now regarded as untreatable must be developed. No one should rest until such treatments reach the bodies of the people they may save.

— Mark Harrington, “The Melting Bureaucracy,” OutWeek Magazine No. 3, July 10, 1989, pp. 35, 54.

#outweek #issue 3 #lgbt history #hiv aids #act up #mark harrington #political scence #drug research #azt #burroughs wellcome #fda #pneumocystis carinii pneumonia #cmv retinitis #ellen cooper #anthony fauci #frank young #dhpg #niaid #cdc