Drugster - Clinical Research Insider No. 10 English

Ivonne Cid

STAFF DIRECTORY

Marco Cid

Carmen de la Rocha

Wendy López Romero

Dante Alducin

José Torres Sales

Valdés Calleja

EXECUTIVE

DIRECTOR

Yesika Muñoz

Jessica Mendoza

Ailyn Cerda

Evelin Bernal Pavel Moreno

Ivette Venegas Victoria Arnauda

Claudia Mejía Morales

Chris De Savi

Katkerine Daneri

Siva Kumar BUDDHA

Rogelio Marín

Ana Villaseñor-Todd

Irene Licona

Erick M. Rodríguez Castro

Miguel A. Robledo Valdez

Lucrecia Carrera Quintanar

Guillermo Moreno-Sanz

Mauro Orozco

Orígenes Romero

Rick Ruiz-Dana

yesika.munoz

@droxhealth.com

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@droxhealth.com

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@droxhealth.com / 33 16 96

22

CENTRAL RESEARCH

Quality of medicines

Rodrigo Martínez Espinosa, MSc. PhD.

FDA Novel Drug Approvals

2022

Chris De Savi, PhD

Medical products of substandard quality, the main affected: the patient and the family

Q. F. Katherine Daneri

Predictive analytics in pharmacovigilance

Dr. Siva Kumar BUDDHA

36

RANKING INSIDER Page

The most counterfeited drug groups in the world

38

BUSINESS & DEVELOPMENT

Anti-obesity drug Semaglutide Approved by FDA After Demonstrating Efficacy in Teens

Carmen de la Rocha, PhD

Drug to be tested in humans to treat obesity and diabetes

Wendy López Romero, PhD

Moderna-Merck Alliance: Together for a Skin Cancer Vaccine

Claudia Mejía Morales, PhD

Mexico, spearhead of the scientific economy in Latin America. Interview with Rogelio Marín

48

SCIENCE TODAY

Alcoholic hepatitis, the excessive insult and disinterest in our liver health

Dr. Ana Villaseñor-Todd Myelofibrosis, How much do you know about this type of blood cancer?

Lic. Irene Licona

Is there a relationship between diet and oral health?

NS. Erick Manuel Rodríguez Castro, NC. Miguel A. Robledo Valdez and PhD in C. Lucrecia Susana Carrera Quintanar

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security mechanism The

Concern for man himself and his safety must always form the chief interest of all technical endeavors

- Albert Einstein

What can and should never be done with the power of science is dangerously fascinating and complex. A civilization can measure its development through the scientific advances it develops to meet its needs, including health protection, however, in the wrong hands, knowledge can become perverse. Is it necessity that pushes us to take easy but wrong paths, or is it the creation of needs that feeds human endeavor and industry?

Given the alarming evidence of counterfeit medicines worldwide, and because of the new and persistent ills that afflict health, we have arranged this issue to give voice to experts in the field of regulation, manufacture and monitoring of all processes that involve the creation and good management of medicines, as well as the entities involved.

In a timely manner, the quality of the drugs and the phases involved in their manufacture will be analyzed from different perspectives, from their initial conditions to their post-marketing, in addition, we offer a display of points of view on the so-called generic drugs, biosimilars, substandard or lower quality drugs. We will also explore the FDA’s latest drug approvals, and how to use predictive analytics and artificial intelligence to detect adverse drug reactions.

Our constant mission as human beings is to sensibly collect the knowledge of those who bring new advances in science, to make it prevail and, in due course, to perfect it. What would the world be without entities that are responsible for the regularization of science for the common benefit? Without the researcher or scientist who dedicate their lives to the study and discovery of new molecules or medical devices... If there were a lack of confidence and security in the processes and in the health professionals, no one could think serenely, and the institutional field would be anarchic. What is the situation in Latin America? What is the relationship between India and Mexico and the medicines consumed in the rest of the world?

Making safety a habit involves making informed decisions, with the component of rigor and the implementation of values in each act. In our current scenario, where the world is constantly evolving and perfecting itself, ethics and progress must converge on the same plane.

They manage to diagnose autism through a single hair

Autism spectrum disorder (ASD) is characterized by disturbances in communication and social interactions, restricted behavior patterns, hypersensitivity, and hyposensitivity. It is associated with significant impairment in social, occupational, and other important areas of adaptive functioning. It is commonly diagnosed from 14 months to three years of age; however, it can be present from birth. Its assessment is carried out through the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which has clinically validated scales and checklists. Although genetic factors are usually the main reason for the appearance of ASD in most cases, in recent years various prenatal (viral infections, alterations

in the immune system, zinc deficiency) and postnatal (exposures to drugs, certain foods or heavy metals) environmental risk factors have been studied alternately, which have also been significantly interrelated to the development of autism.

In a Japanese national prospective study called JECS, focused on the investigation of environmental factors that could affect the health and development of children, where 82,413 participants were followed from conception to three years of age, of which 220 (and 110 cases with ASD) were selected; in parallel, studies were conducted in Swedish participants (national

cross-sectional study with twins, n = 138 and 42 cases with ASD) and American (cross-sectional study of a single clinical center with neurotypical population, n = 128 and 23 cases with ASD). The collected hair samples were analyzed by mass spectrometry of elemental metabolism to identify biomarkers of ASD and then a machine learning algorithm was trained with 80% of the generated data and tested on an exclusion set of the remaining 20% of randomly selected data, to compare the diagnostic result of the algorithm with respect to the reference of the current gold standard of formal clinical diagnosis of ASD according to the DSM-5.

To characterize the model’s performance, they constructed receiver operating characteristic (ROC) curves. According to the optimal criterion, the model yielded a sensitivity of 96% (95% CI: 82-100%), specificity of 75% (95% CI: 64-85%), specificity of 81% (95% CI: 72-89%) and overall accuracy (Youden index) of 0.71. Regarding the performance of the model stratified by sex and age categories, there was no statistical significance regarding the overall performance of the device.

The findings of Austin et al., emphasize that the dynamics of elemental metabolism are systemically dysregulated in patients with ASD and that the biomarker signatures generated allow identifying the onset of ASD with as little as one month of age. More than a year after the launch of StrandDx-ASD (as the model has been named), it has FDA approval, and its sponsor Linus Biotechnology has received 16 million dollars for the financing of the generation of more clinical data to demonstrate its diagnostic accuracy.

Abbreviations:

DSM-5: Diagnostic and Statistical Manual of Mental Disorders, fifth edition. JECS: The Japan Environment and Children’s Study.

ROC: Receiver Operating Characteristic. CI: Confidence Interval.

Sources

Murray, M. J., Mayes, S. D., & Smith, L. A. (2011). Brief report: excellent agreement between two brief autism scales (Checklist for Autism Spectrum Disorder and Social Responsiveness Scale) completed independently by parents and the Autism Diagnostic Interview-Revised. Journalofautismanddevelopmentaldisorders , 41(11), 1586-1590.

Grabrucker, A. M. (2013). Environmental factors in autism. Frontiersinpsychiatry 3, 118.

Austin, C., Curtin, P., Arora, M., Reichenberg, A., Curtin, A., Iwai-Shimada, M., ... & Nakayama, S. F. (2022). Elemental dynamics in hair accurately predict future autism spectrum disorder diagnosis: an international multi-center study. Journalofclinical medicine 11(23), 7154.

Dr. Wendy López Romero,

Research and Development Analyst at Drox Health Science. PhD in Innovation in Medical and Pharmaceutical Biotechnology. Master in Molecular Biology.

Writing by

1.

2.

3.

Claudia

Cough syrups linked to death

On October 5, 2022, the WHO issued an alert (No. 6/2022) on pediatric medicines of substandard quality. These are four syrups to treat coughs and colds in children. A second alert (No. 7/2022) of pedia-tric medicines was issued on November 2 for eight products such as cough syrups and acetaminophen drops. In both cases, laboratory tests on the syrups confirmed the presence of unacceptable amounts of diethylene glycol (DEG) and ethylene glycol (EG). The drugs mentioned in the alerts have been associated with the deaths of at least 70 children in Gambia, Africa, mostly under 5 years of age, 18 children in Uzbekistan and 199 children aged 7 to 11 years in Indonesia [1,2], in most cases acute renal insufficiencies occurred. Many of these syrups contain Paracetamol (acetaminophen) as an active ingredient, which contributes to the treatment of pain, fever and general malaise, however, this compound is poorly soluble in water and requires solvents such as glycerol or propylene glycol to provide the liquid base; some manufacturers choose to replace glycerol with compounds such as diethylene glycol

(DEG) or ethylene glycol (EG), both of which tend to be cheaper. DEG and EG are organic compounds miscible in water with a sweet taste and commonly used as industrial solvents and in the manufacture of antifreeze, dyes and brake fluids. DEG is metabolized to insoluble oxalic acid, and EG to glycoaldehyde, glycolate, glyoxylate, and oxalate. The accumulation of the resulting compounds in the body induces kidney damage and failure, cardiopulmonary problems and often death. This type of episode has continued to be recorded since 1937 (sulfanilamide Elixir) [3], so control must be increased in the proper development of new products considering Good Manufacturing Practices, and above all taking care of the health of the population.

Umar, T. P., Jain, N., & Azis, H. (2023). Endemic rise in cases of acute kidney injury in children in Indonesia and Gambia: what is the likely culprit and why?. Kidney

FDA Approves Controversial Drug-Slowing Alzheimer’s Progression

On January 6 of this year, the FDA approved the biologic drug lecanemab for the treatment of Alzheimer’s disease through an accelerated process. Although the results of their clinical studies indicate a delay in disease progression in patients who received it, the risk of adverse events and the high cost of the drug appear to outweigh the benefits.

The results of the phase III study in which more than 1,000 people diagnosed with the disease participated concluded in a decrease in the amyloid markers characteristic of the pathology in the group that received the asset, this was accompanied by a moderate decrease in the progression evaluated in cognitive abilities and function compared to the group that received placebo. However, the authors report that these findings have been accompanied by adverse events, as well as concluding the need for longer studies to determine the efficacy and safety of the biologic.

Among the adverse events observed are inflammation and bleeding of the brain, so the FDA, with

approval, issues an alert label suggesting three nuclear MRIs during the first six months of treatment as medical surveillance measures, as well as a contraindication of anticoagulants.

On the other hand, the cost of the drug, without considering the MRIs and expenses associated with intravenous infusion (the route by which it must be administered), is estimated at about $ 25,000 per year.

While the approval of the drug represents an alternative for the treatment of people living with Alzheimer’s, which could translate into more and better quality time, the accelerated approval process in the face of worrying safety evidence should probably not be considered.

Sources

1.

2.

van Dyck, C. H., et al (2023). Lecanemab in Early Alzheimer’s Disease. TheNewEnglandjournal ofmedicine 388(1), 9–21. Available at: https://doi.org/10.1056/NEJMoa2212948

FDA approves new antibody to slow alzheimer’s disease, even as safety concerns linger (6 Jan, 2023) Science (Accessed: January 10, 2023). Available at: https://www.science.org/content/article/ fda-approves-new-antibody-slow-alzheimer-s-disease-even-safety-concerns-linger

Writing by:

Director of Research and Development at Drox Health Science. PhD in Biotechnology, Master in Biochemical Engineering. Member of the National System of Researchers level I.

Dr. Carmen de la Rocha,

IS

CHEAP EXPENSIVE

Marco Cid

CEO Drox Health Science – CEO Clinical Research Insider

Chemist-pharmacist Biologist from La Salle University, MBA from ITESO, postgraduate in clinical research from York College, and Senior Management from the InnovAD Program of IPADE. Expert in research and development of drug products; entrepreneur, founder of several for-profit and non-profit associations, and creator of a private equity investment company.

In this edition of Clinical Research Insider, we will review the topics related to drugs marketed with no proven efficacy or safety in their development phases. This is a common matter in countries that do not yet have a robust health surveillance system; You always end up acquiring the cheapest option or the option available in the local market, beyond the constant search to find out if that drug or medical device obtained the permits required to be sold in that specific domestic market.

It seems to us to be an issue of the utmost importance, for it can become a public health issue; Drugs or medical devices that are apocryphal, or with little scientific validity, can put the lives of the people who consume them at risk. Without data on the efficacy and safety profile of the drug, dietary supplement, or medical device, the risk of severe adverse events, lack of efficacy, or drug interactions is in doubt.

Our sister companies have spent lots of effort and dedication in developing new strategies for pharmaceutical companies or medical device developers to generate efficacy data and build a safety profile for each product intended for international markets. In addition, there are real efforts by regulatory entities to fight against this phenomenon.

The efforts to push for good practices in the development of medicines must come from various spheres, starting from the developers themselves to those who provide scientific data and the public avoiding the purchase of these products.

Within social wisdom, it is believed that certain products derived from plants and animal oils can be beneficial to health, as they have been used since ancient times to cure various ills. While this may be correct, when we work on developing a product derived from those mentioned sources, it is important to know that the alkaloid extracted is no longer in its natural state and the percentage of it may vary; We do not know what the maximum effective dose may be to achieve a therapeutic effect. Will we be aware of what we could cause by bringing such a product to market?

I end with an invitation to all those business owners or entrepreneurs who are thinking of placing a pharmaceutical product or medical device on the market, rest assured that testing the safety and efficacy of the product will give them in addition to the necessary approvals in all the countries in which they want to enter, as well as necessary data to sustain or develop your competitive advantage over your competitors.

And for the end users of the products? We invite you to investigate the product you have purchased, review how its effectiveness was proven, and what kind of safety profile has. Only then we will find better products on the market.

And the dose makes the poison

I like to see the Riedel glasses shine under the right light. It highlights the intense reds of Malbec and even makes a Pinot Noir more palatable if it is served in the glass destined for such a grape. What not many people know is that they created a special glass to drink CocaCola, designed to extract and enjoy all its properties. Something peculiar taking into account the increasingly frequent campaigns against the mythical drink, there is more and more awareness of the effects that its consumption can have.

I wonder if John Pemberton, a former Confederate soldier, would have imagined even half the repercussions of his creation, originally conceived as a life-long stimulant and aphrodisiac. At first, it was simply a type of alternative medicine to cure his addiction to heroin, which at that time could be bought in any pharmacy. Pemberton’s obsession was to create the final medicine and he decided to add to Coca-Cola nothing more and nothing less than cocaine (hence its name), however, when its addictive potential was discovered, it was replaced by caffeine.

Since then, Coca-Cola has gone from being a lowquality medicinal product to a refreshing drink and being demonized as unhealthy, a symbol of American hegemony and much more... Beyond how much we may hate or love Coca-Cola, to the extent of tasting

it in Riedel glasses, it gives us an important lesson: what today is considered a novel medicinal product or a “superfood supplement”, in a few years can be repudiated, loved or destined for different uses. It all depends on the context.

Something that few people know is that everything we consume and even the air we breathe has a certain toxicity. The only way not to age would be not to breathe and that would kill us in a few minutes. Additio-nal toxicity will always be discovered from anything we consume because we have more and more refined methods and different measurement guidelines.

As the mythical alchemist Paracelsus, father of toxicology, said: “Dose sola facit venenum” or, “Only the dose makes the poison”. What do we have to do as consumers? have some common sense to consume medicines only when they are prescribed to us and avoid miracle products because they do not exist. Something so simple to say is much harder to achieve. We always like to take shortcuts to get results and that is impossible, deriving two scenarios from this. The first is the lack of information and education, which should be avoided at all costs. The second is that, although people have such tools, they prefer to ignore common sense with the proper consequences, that in my opinion is natural selection and cannot be stopped.

In the meantime, I’ll continue to enjoy a Riedel glass Coca-Cola from time to time.

QFB with the Specialization in Leading People and Teams program at the University of Michigan. He has 12 years of experience in Clinical Research. Founder of Blast! Academy and host of the podcast Ruido Blast!

The challenge of drug manufacturing in Latin America

While it is true that there is legislation in all countries of the region that obliges the doctor to prescribe medicines with generic name to his patients, it is also true that doctors prescribe brand-name medicines without asking the patient if he is able to access them when he approaches a pharmacy to acquire them. In middle- and lowincome countries, a generic market has developed over the years that largely tries to reduce the patient’s out-of-pocket expense without sacrificing the quality of treatment and producing the same benefit as that produced by the original molecule.

The challenge for low- and middle-income countries is how to ensure that these so-called brandname generic or copy-bearing drugs meet efficacy and patient safety requirements and achieve the expected outcomes. In the Latin American region, for example, most research laboratories have developed an interesting portfolio of branded generics, produced by them in their parent companies that, known for their good manufacturing practices, meet legal requirements, added to the trust of the brand.

In the case of local laboratories, they buy the active ingredients from markets such as China, India and others, which entails lower production costs reflected in the direct cost to the patient. With India being the most important generic market globally, all its products are expected to be GMP certified. In these reasons lies its preference of use and the significant growth of the market in the region. In the same sense, governments have advanced with legislation that requires manufacturers of some products to demonstrate, through bioequivalence and biosafety tests, that both the original and the copy are exactly the same in their pharmacological

properties. In addition, regional pharmacovigilance initiatives allow for drug pathways and postapproval support. Much has been done, but there are still challenges to be faced.

In the region, there is a significant growth of socalled Biosimilars, which are medicines that have demonstrated this behavior, after the expiration of protection patents. On the other hand, the increasing prevalence of chronic, autoimmune, genetic, and cancer diseases has driven this market in middle- and low-income countries. This forces governments to design regional roadmaps that allow for expeditious approval, but without sacrificing their security. From this perspective, the heterogeneity of legislation in the region, the different ways in which they are approved, the burden of disease in each country and financing affect this issue.

However, to address this issue, regulatory bodies should follow a different route of approval to other types of medicine, such as generic drugs, for example, taking into account the requirements of the EMA, FDA and WHO; which will allow its use safely in patients avoiding some quality gaps with respect to the origin of these Biosimilars

José Torres Sales MD, MBA, DBA© LATAM Strategic Medical Director FARMACON GLOBAL jose@farmasc.com

Interview with

Dr. Juan Carlos Arana Ruiz

High Specialty Physician from the National Institute of Respiratory Diseases (INER); focused on Continuing Medical Education and Development of Clinical Research Opportunities. Currently, Doctor at the ABC Hospital and the Clinic of Excellence of Rheumatology, Mexico.

An approach to the unknown; Rheumatic Diseases explained by an expert

» Some of the most enigmatic and little-known conditions of medical science in general, without a doubt, is the set of rheumatic diseases. According to the World Health Organization (WHO), musculoskeletal disorders comprise more than 150 diseases affecting the locomo-tor system, and low back pain is the most common cause of disability in 160 countries(1).

To imagine its social scope, in addition to impacting health and being one of the specialties that have experienced the greatest demand in diagnosis and treatment in recent years, rheumatic diseases are one of the main causes of early retirement, absenteeism, and job loss worldwide.

On this occasion, we have the special collaboration of Dr. Juan Carlos Arana Ruiz, who shares with us his knowledge and experience in the field to elucidate the most frequent doubts about rheumatic diseases and their particularities.

To introduce ourselves to the subject, Dr. Juan Carlos Arana,

what are rheumatic diseases and what are the main conditions that make them up?

They are a large and heterogeneous group of conditions ranging from painful syndromes of degenerative origin and chronic nature, which affect various structures of the musculoskeletal system (joints and their components, bones, muscles, etc.), to diseases where the central axis is a “disorder” in the processes of inflammation or components that usually protect us from external aggressions (mainly microorganisms) and internal (cancer), that is, the immune system, which by various very complex mechanisms, lead to the self-destruction of very varied components of the organism, from various types of joints to vital organs. (3-6)

Which population is more likely to suffer from rheumatic disease?

The answer is as diverse as rheumatic diseases. Although in general, they tend to affect women much more frequently (biologically speaking), being much more prone, especially during their reproductive years (from menarche to the arrival of menopause), which we call

autoimmune. However, the tendency to suffer from autoinflammatory diseases, although usually a little more common in men (e.g. ankylosing spondylitis), evidence shows that they are rather diagnosed late in women, more frequently. (4-6)

What are the latest advances in clinical research and drug development in the area of rheumatology?

Unquestionably, Rheumatology has suffered an explosion since the 90’s, with the advent of disease-modifying drugs (DMARDs) of a biological type, which are strategically designed against molecules responsible for triggering and perpetuating self-injurious inflammatory processes, such as TNF inhibitors (one of the most important molecules responsible for inflammation), also called anti-TNF, to mention some of the many examples now available, even for pathologies that were previously conside-red practically untreatable, when there was no response to traditional synthetic DMARDs (such as methotrexate, leflunomide, etc.) or the most toxic immunosuppressants (cyclosporine, azathioprine, etc.). Such is the case of spondyloarthropathies, for which there is now a wide therapeutic weapon with efficacy that had never before been seen in problems such as psoriasis or

ankylosing spondylitis (anti-IL17A, anti-IL12/23, etc.). However, the new revolution is made up of small molecules (JAK-STAT inhibitors), which make it possible to treat even as monotherapy, for conditions that have not responded to more economically accessible drugs. There are still multiple investigational drugs that have at least high biological plausibility, however, that will be defined by the future to come. (7)

On this subject, I would like to comment that there are now techniques that combine nanotechnology and bioengineering with molecular biology and immunology, at a level that seems like science fiction, such as CAR-T cells, which literally allow editing “at ease”, according to the most plausible target molecule,

to achieve remission in conditions that were previously considered untreatable or that lose any response to available treatments.

Today, this is even achieved in people with lupus. Stem cell transplantation is also promising new possibilities every day in diseases as difficult to treat and as aggressive as systemic sclerosis. (7-11)

» In this same atmosphere of advances in the area, people with rheumatic diseases have benefited through innovative and patient-centered research, from basic research using disease models to clinical research that explains new tests or treatments. Based on this,

It is precisely the research protocols (clinical trials) that have allowed revolutions in treatment. It is important for patients to know that when they are suggested to participate in a protocol, it is because their chances of response have been diminished and are a biologically very plausible option, that is, they have already been tested extensively and meticulously in cellular media, in animal models, and in healthy patients, to know their safe dose. Depending on the phase of the protocol, efficacy will be investigated and this is where many patients could benefit from less toxic and more potent alternatives when what is currently available on the market is not enough. (6-12)

How frequent is counterfeiting of medicines against rheumatic diseases and what are the consequences of their consumption?

Unfortunately, malicious people are not uncommon, so you must be very careful that any drug, even the one that “promises” to be of natural origin (in fact this is usually an alarm when they claim to be 100% natural since nothing encapsulated is 100% natural by its very essence), since its origin is dirty money, in addition to having another interest than economic gain, at the expense of people’s suffering. They must always make sure to use and consume drugs purchased in legally established places and certified by the corresponding Health Authority.

what advantages could a person with a rheumatic disease obtain by entering a clinical research protocol?

Never consume anything that has violations in their seal or does not follow the extremely strict standards of quality. Consequences, when there are any, the least serious, is simply the lack or loss of effectiveness, but we have even come to see contamination by carcinogens and infectious agents, the latter, with sometimes catastrophic consequences such as the loss of an organ due to infection. (17)

» Although at least five million people worldwide have a form of Systemic Lupus Erythematosus(2), it is currently a very poorly understood pathology compared to other diseases due to the complexity of its symptoms and treatments. As for this disease,

what do you think are the best treatment options and management strategies for people with Lupus?

The first and most important strategy is proper and early diagnosis. At least 70% of patients who come to my office with a suspected diagnosis of lupus do not actually have lupus. This is a disease that became fashionable because it was suffered by a famous person, but it is fortunately rare, affecting less than 0.05 to 0.1% of the world’s population, especially in its most severe forms. In this regard it is important to note that each patient with lupus is very particular, I have never seen two patients exactly alike, even though there are classification criteria that have become ostensibly easier to use for diagnosis; a rheumatologist is required to certify the diagnosis, often in a joint effort with other specialists. The treatment should always be orchestrated by a specialist in Rheumatology,

since it is complex, still poorly distinguishable, except for the most severe forms, and in continuous evolution. Today we have two approved biologics, belimumab and anifrolumab which, however, are not useful for any patient. As well as an old acquaintance, rituximab, although it does not have the approval, has been used in an artisanal way, although it is also not effective in all patients, so a treatment directed by objectives is recommended where some glucocorticoid is used as little time as possible (as bridge therapy), which allows improving the quality of life of the affected person, as well as ensuring complete remission (ideally) of the disease. (12-13)

What is drug-induced lupus?

Excellent and accurate question, given that precisely many patients who experience this problem, is simply due to some drug that generates a disordered immune response and its interruption alone is enough to end the problem in at least 90% of those who suffer from it. The most common in favoring it are some antiarrhythmics such as amiodarone or propafenone, as well as antihypertensives such

as alphamethyldopa or hydralazine. But even in TNF inhibitors it has been described, by the way, that rarely this type of lupus affects beyond skin, joints and if anything, blood cells, but in the case of the latter, up to 8% come to have kidney involvement. It should be noted that the chance of a person developing this type of disordered response is very low, so they should not panic if they are told and do not have any autoimmune diseases in the family. As I said, it usually remits in the vast majority, with simply stopping the drug and strangely it is serious. (15-16)

Finally, dear Dr. Arana, what is the role of genetics in rheumatic diseases?

Excellent question, although its answer is extremely heterogeneous, as heterogeneous are autoimmune diseases (where there is a large number of genes involved, and will depend on the presence of one or more of these, as well as polymorphisms in these genes, eg, in lupus only more than 30 genes have been described, and the agreement in identical twins is 24% - 35%) and autoinflammatory (these with greater genetic predisposition, for example, those of Norse ancestry with the presence of HLA-B27). Genetic penetrance is higher in chronic-degenerative diseases, such as osteoarthritis of the hands, where the risk is as high as 87% of suffering from it in identical twins. (12-14)

References

World Health Organization (WHO) 8 February 2021. Musculoskeletaldisorders . Accessed December 15, 2022. Retrieved from: https://www.who.int/es/ news-room/fact-sheets/detail/musculoskeletal-conditions

Fundación Lupus de América. Last updated: February 23, 2022. Hechosyestadísticassobrelupus.Accessed December 15, 2022. Retrieved from: https:// www.lupus.org/es/resources/hechos-y-estadisticas-sobre-lupus

Lin, C.M.A., Cooles, F.A.H. & Isaacs, J.D. Precision medicine: the precision gap in rheumatic disease. NatRevRheumatol18 , 725–733 (2022). https://doi. org/10.1038/s41584-022-00845-w

Stovall, R., van der Horst-Bruinsma, I.E., Liu, SH. et al. Sexual dimorphism in the prevalence, manifestation and outcomes of axial spondyloarthritis. Nat RevRheumatol18,657–669 (2022). https://doi.org/10.1038/s41584-022-00833-0

Raine C, Giles I. What is the impact of sex hormones on the pathogenesis of rheumatoid arthritis? FrontMed(Lausanne).2022 Jul 22;9:909879. doi: 10.3389/fmed.2022.909879. PMID: 35935802; PMCID: PMC9354962.

Cutolo M, Villaggio B, Craviotto Ch, Pizzorni C, Seriolo B, Sulli A. Sex hormones and rheumatoid arthritis, AutoimmunityReviews.2002;1(5):284-289. ISSN 1568-9972.

Shirota Y, Illei GG, Nikolov NP. Biologic treatments for systemic rheumatic diseases. OralDis.2008 Apr;14(3):206-16. doi: 10.1111/j.16010825.2008.01440.x. Epub 2008 Feb 14. PMID: 18282173; PMCID: PMC2766248.

Conti F, Ceccarelli F, Massaro L, Cipriano E, Di Franco M, Alessandri C, Spinelli FR, Scrivo R. Biological therapies in rheumatic diseases. ClinTer. 2013;164(5):e413-28. doi: 10.7417/CT.2013.1622. PMID: 24217844.

Volkmann, E.R., Varga, J. Emerging targets of disease-modifying therapy for systemic sclerosis. NatRevRheumatol15,208–224 (2019). https://doi. org/10.1038/s41584-019-0184-z

Bruner V, Atteno M, Spanò A, Scarpa R, Peluso R. Biological therapies for spondyloarthritis. TherAdvMusculoskeletDis.2014 Jun; 6(3):92-101. doi: 10.1177/1759720X14535512. PMID: 24891880; PMCID: PMC4040940.

Mackensen, A., Müller, F., Mougiakakos, D. et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. NatMed28,2124–2132 (2022). https://doi.org/10.1038/s41591-022-02017-5

Samotij D, Reich A. Biologics in the Treatment of Lupus Erythematosus: A Critical Literature Review. BiomedResInt.2019 Jul 18; 2019:8142368. doi: 10.1155/2019/8142368. PMID: 31396534; PMCID: PMC6668536.

Guerra SG, Vyse TJ, Cunninghame Graham DS. The genetics of lupus: a functional perspective. ArthritisResTher.2012 May 29; 14(3):211. doi: 10.1186/ ar3844. PMID: 22640752; PMCID: PMC3446495.

Magnusson K, Turkiewicz A, Haugen IK, Englund M. The genetic contribution to hand osteoarthritis. OsteoarthritisCartilage.2022 Oct;30(10):1385-1389. doi: 10.1016/j.joca.2022.06.011. Epub 2022 Jul 14. PMID: 35843480.

He Y, Sawalha AH. Drug-induced lupus erythematosus: an update on drugs and mechanisms. CurrOpinRheumatol.2018 Sep; 30(5):490-497. doi: 10.1097/BOR.0000000000000522. PMID: 29870500; PMCID: PMC7299070.

Solhjoo M, Goyal A, Chauhan K. Drug-Induced Lupus Erythematosus. [Updated 2022 Apr 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441889/ Palacios García, SA. (2020). La otra pandemia. RevistadelaOFIL,30(3), 178. Epub 05 de abril de 2021. https://dx.doi.org/10.4321/s1699714x2020000300004

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Rodrigo Martínez Espinosa,

MSc. PhD.

Quality of medicines

The quality of medicines is an issue of great importance in human health. At present, methodologies, disciplines and institutions have been generated whose objective is that the population has safe and effective medicines, with precise uses and in safe environments. The reason for this article is to recall the most important elements to guarantee the quality of medicines in three stages: Development, Approval and Marketing.

Development

When a pharmaceutical company or laboratory intends to search for new drugs, its main concerns are safety and efficacy, a quality drug during preclinical and clinical development will be the one with an acceptable degree of safety and efficacy. These two elements are analyzed during preclinical trials, usually in vitro cell cultures and in non-human animal models (mice, rabbits, monkeys, etc.). In these models, toxic doses of the molecules studied are calculated, as well as possible therapeutic doses. Only in the case that low toxicity is demonstrated, even at high doses, the study can continue with the Phase clinical studies.

Phase 1 studies primarily evaluate the safety of the drug, as well as potential therapeutic doses. These trials use a small number of individuals, usually healthy. If safety is demonstrated in Phase 1, we proceed to Phase 2, where the number of participants is increased, the doses with possible therapeutic effects are evaluated and the presence of adverse events of the drugs studied is thoroughly analyzed. It is important to note that all drugs have associated adverse events, this is natural when dealing with molecules with physiological effects, the important thing is that the adverse events of the compounds studied are not more serious than the disease that is trying to combat and that, in general, they occur with low frequency. Finally, Phase 3 is a large study, with a high number of research subjects and where the efficacy and safety of the drug will be tested at clinically relevant doses.

Approval

If a medicine has demonstrated its efficacy and safety in clinical trials, it can be submitted to the corresponding health authorities for approval in order to be marketed. The authorities that regulate

Medical Advisor - Medical Manager at Carnot Laboratorios. Specialist in Genetics and Molecular Biology of Complex Diseases.

the drugs are in charge of evaluating the existing scientific evidence on the drug to be approved, particularly the Phase 3 trials. In the United States this authority is the Food and Drug Administration, FDA, in Europe it is the European Medicines Agency, EMA for its acronym in English, and in Mexico the Federal Commission for the Protection against Sanitary Risks, COFEPRIS. It is very important to note that these agencies have as their main objective to protect the health of the population, so they particularly evaluate the safety of medicines.

In general, regulatory agencies have groups of experts that analyze, objectively and critically, the scientific information provided by the applicant for approval, which are usually the laboratories that developed the molecule or the company that will commercialize it. An important point of the approval process is that the applicant has to specify the dosage (how much and how to administer the drug) as well as the therapeutic indication to which it is directed. The role of the regulatory entity is to approve or reject the application; In the first case, sanitary registration is granted to the drug, which allows its manufacture and commercialization in the country.

Another important area where the health authority intervenes is in the manufacture of medicines, every manufacturing plant has to comply with a series of minimum standards and regulations for its operation. This is essential to ensure the quality of a drug, since, as we know, a drug not only contains the active substance, responsible for the therapeutic function, but also a number of other compounds that provide stability, release, taste, etc. Each of them must have the appropriate quality, purity and quantity, which guarantee the efficacy and safety of the drug. The manufacturing process of the drug is a key step in ensuring its quality.

Marketing

Although it seems that, by demonstrating safety and efficacy in clinical trials and obtaining sanitary registration and production approvals, the quality of a drug is already guaranteed, this is not true. Storage and distribution processes are critical steps, all medicines have to remain in specific conditions, temperature is a very relevant factor: below -15/-20 °C is frozen, between 2 °C and 8 °C refrigerated, between 8 °C and 15 °C is cold or cool and between 15 °C and 25 °C room temperature. Another important factor is exposure to sunlight,

many chemical compounds are very sensitive to sunlight and have to be protected from it, for this manufacturers use dark packaging, amber jars or double packaging, however, this is not exempt

from the need to store away from direct sunlight. The physical integrity of containers, packaging or bottles is something that always has to be corroborated, any medicine with damaged packaging (broken, wet, open, discolored, deformed, etc.) should not be used, there is a risk that the quality is compromised. Finally, storage time is essential, all medicines have an expiration date, after which their use is not recommended. At present the activity of surveillance of the quality and safety of medicines is known as pharmacovigilance, this is the responsibility of the companies that produce medicines, but also of health professionals and health institutions, when it is taken responsibly, pharmacovigilance in a powerful tool to ensure the quality of medicines.

It is true that sometimes the expiration or mishandling of medicines causes their lack of effectiveness and not directly new safety risks or adverse effects different from those known, however, in some cases, serious health risks may appear, such as contamination by bacteria or fungi. One of the potentially most serious cases in the quality of medicines is their falsification or alteration, unfortunately, it is not uncommon for altered or counterfeit medicines to be marketed clandestinely, which represents a serious health risk.

What about the quality of generics and biosimilars?

Generic drugs are those that contain the same active ingredient(s) as another medicine already registered. When a company obtains registration for a novel drug, that is, whose formulation of active ingredients was not previously used, this drug is known as a reference drug, which has a period of commercial exclusivity, usually about 10 years, from obtaining registration, in which only the company that owns the registration can produce the drug. Once this period expires, any

other company can manufacture the medicine in question, as long as it meets the requirements of bioequivalence and manufacturing.

Bioequivalence is the key to ensuring that a generic drug (other than the reference drug) makes no significant difference in the rate and degree to which the active ingredient or active fraction is available at the site of action of the drug when administered at the same dose and under conditions similar to the reference dose. Therefore, when we talk about an equivalent generic, it is guaranteed that they have the same chemical-pharmaceutical quality, potency or concentration and safety. According to the legislation of each country, the parameters and definitions for bioequivalent generic medicines may vary, but in general, we can say that the use of generic medicines that have the appropriate permits is as safe and effective as the reference medicine.

On the other hand, biological drugs, also known as biotechnology, are subject to the regulations of the authorities, although the analysis and evaluation techniques may be different from chemical drugs; biologics need to guarantee safety, efficacy and quality. Like generics, in the case of biologics, there are biosimilars, non-original drugs that claim to have the same therapeutic effects and safety as reference biologics. In some cases, particularly with some monoclonal antibodies, this can be difficult to achieve, however, thanks to biotechnological advances, a large number of high-quality biological medicines are now available.

Why are you here?

In this fast-paced and global world there is a reason why all professionals involved in the pharmaceutical, health or research industry wake up eager to work every Monday, to be more creative, to improve some process in the company where we collaborate, to give the best of ourselves and to discover how capable we are and how far we can go.

I will tell you a little bit of my story and the reason why I am here.

When I was a child I dreamed of being a sailor like my father, however, life took us down a very different path. It all started with my younger brother's diagnosis of Duchenne Muscular Dystrophy.

It is undoubtedly one of the most difficult news to receive from any perspective, as a patient, as a parent and, in my case, as a sibling. From that moment on, I could see my parents worried and even more so, busy informing themselves day and night about what was the solution for this condition, which currently does not exist.

It was in some scientific articles where we began to learn about the industry and clinical trials, but unfortunately in our country it

M.B.A. Hugo J. Lira Buendía CEO Clinical Health Research Institute

not viable 20 years ago. That was when we got down to work. From that time until now I have tried to do everything possible and what is in my hands to work from my trench and do my bit, to try to support every patient and every family that was related to this disease. So, what is this trench?

Together with my father, we started to work on establishing a research site with the objective of bringing "Duchenne" clinical trials to our country, an objective which we have accomplished for 8 years now. The Clinical Research Institute for Health and the IMAO Foundation for Duchenne boys were created and today we have in Mexico the research on DMD, we also support families psychologically as a means of containment of what we as a family have lived, we have a database of patients and we try to find the best trial for them, we have international agreements to attend patients from LATAM in our site, this and many other activities is what currently makes me want it to be Monday every day.

We all have a life story probably related to what we do on a daily basis; what we do most is who we are, it is part of our being and we should be proud of it. And you, why are you here?

CSO Partner at Curie.Bio

FDA Novel Drug Approvals 2022

That is a wrap for 2022! And another year of relentless drug discovery.

For you hard-core drug discovery, here are the list of 2022 novel FDA approved drugs, 37 NMEs so far, down from 2020 and 2021 (53 & 50 approvals, respectively). Before we start talking about a decline in innovation, it has been a turbulent year economically and the decline can be attributed to the COVID-19 pandemic. Total approvals have been higher over the last decade than previous.

It has been a BIG year for gene therapy. Gene therapy offers the possibility of a permanent cure for a wide range of inherited disorders. Those approvals include:

Skysona, is used to treat cerebral adrenoleukodystrophy, a rare disease in boys that allows very long chain fatty acids to accumulate in the brain which causes severe disability or death. It is made specifically for each patient, using the patient’s own blood stem cells and adds functional copies of the ABCD1 gene to the patient’s cells; bluebird bio.

Zynteglo, is used for the treatment for ß-thalassemia, an inherited blood disorder that leads the body to produce less hemoglobin. To make Zynteglo, the stem cells taken from the patient’s blood are modified by a

virus that carries working copies of the beta globin gene into the cells; bluebird bio.

Hemgenix, is used for the treatment of the clotting disorder hemophilia B. It is a genetic bleeding disorder resulting from missing or insufficient levels of blood clotting Factor IX. Hemgenix delivers a working gene for the clotting protein to the liver, where it is made; CSL Behring.

Adstiladrin, is the first gene therapy for the treatment of bladder cancer; Ferring Pharmaceuticals.

New medicines which were approved in Q422

Krazati, a KRASG12C inhibitor for the treatment of NSCLC; Mirati Therapeutics.

Rezlidhia, an isocitrate dehydrogenase-1 inhibitor used to treat relapsed or refractory AML; Rigel Pharmaceuticals Inc.

Tzield, a humanized anti-CD3 mAb that is used to delay the onset of stage 3 type 1 diabetes; Provention Bio.

Elahere, a folate receptor (FR) alpha-directed antibody and microtubule inhibitor conjugate used to treat FR alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer; ImmunoGen, Inc.

Tecvayli, a bispecific B-cell maturation antigendirected CD3 T cell engager used to treat R/R MM; Janssen Inc.

Imjudo, an anti-CTLA-4 antibody used to treat unresectable HCC in combination with durvalumab; AstraZeneca.

Lenacapavir, an HIV-1 capsid inhibitor for the treatment of HIV; Gilead Sciences.

Mosunetuzumab, a humanized anti-CD20/CD3 bispecific antibody used to treat R/R follicular lymphoma; Roche.

Briumvi, a monoclonal anti-CD20 antibody for the treatment of MS; TG Therapeutics, Inc.

17 of these NMEs can be classified as small molecule drugs.

First-in-Class Drugs 2022

On the other hand, CDER identified 20 of the 37 novel drugs approved in 2022 (54%) as first-in-class. These drugs have mechanisms of action different from those of existing therapies.

These novel first-in-class drugs were:

Camzyos (mavacamten), a mysosin inhibitor, used to improve functional capacity and symptoms in patients with a type of obstructive hypertrophic cardiomyopathy, in which the heart muscle thickens, making it harder to pump blood.

Mounjaro (tirzepatida), a dual GIP and GLP-1 receptor agonist injection to improve glycemic control in adults with type 2 diabetes, as an addition to diet and exercise.

Pluvicto (lutetium 177 Lu vipivotide tetraxetan), a radioligand therapeutic injection to treat adults with prostate-specific, membrane-positive, metastatic, castration-resistant prostate cancer who have received at least two prior therapies, including a chemotherapy. Pluvicto consists of a radionuclide, lutetium Lu-177, linked to a moiety that binds to PSMA, a transmembrane protein that is expressed in prostate cancer.

Sunlenca a first-in-class HIV1 capsid inhibitor, given as tablets and injection for adults with HIV who have previously received many HIV therapies and whose disease cannot be treated with other available drugs. Patients receive Sunlenca in combination with other antiretroviral(s).

Tzield (teplizumab-mzwv), a CD3-directed monoclonal antibody injection to delay onset of Stage 3 type 1 diabetes in adults and pediatric patients with Stage 2 type 1 diabetes.

Voquezna Triple Pak (vonoprazan, amoxicillin, and clarithromycin) and Voquezna Dual Pak (vonoprazan and amoxicillin) are co-packaged products containing combinations of tablets and capsules to treat adults with H. pylori infection, a bacterial infection in the stomach.

Pyrukynd (mitapivat), a pyruvate kinase activator used to treat hemolytic anemia (a disorder in which red blood cells are destroyed faster than they can be made) in adults with pyruvate kinase deficiency, an inherited disorder that causes premature red blood cell destruction.

Kimmtrak (tebentafusp-tebn), a bispecific gp100 peptide-HLA-directed CD3 T cell engager injection, used to treat metastatic or unresectable uveal melanoma, a rare cancer that develops in a part of the eye called the uvea.

Opdualag, an injection to treat patients with metastatic or unresectable melanoma. It contains nivolumab, a programmed death receptor-1 (PD-1) blocking antibody, and relatlimab, a lymphocyte activation gene-3 (LAG-3) blocking antibody.

20 of the drugs approved were to treat rare or “orphan” diseases.

Q. F. Katherine Daneri

Medical products of substandard quality, the main affected: the patient and the family

According to the WHO, 1 in 10 products marketed in low- and middle-income countries are of lowquality standards or counterfeit(1), this indicator does not represent all cases, since no country is exempt from this reality. Unlike counterfeit medicines, substandard products are products that go through a rigorous evaluation before being authorized by the Health Agencies and then in the marketing stage, do not meet the required quality standards or the specifications with which they were registered(2).

Limited access due to economic issues, deficient government systems and without adequate control of safe medical products allows the population to access this type of substandard quality products(3). In addition, these products can be found in illegal street markets, on unregulated websites, and even in pharmacies and hospitals(2).

To put ourselves in context, imagine that we have a family member whose medical treatment represents a life expectancy, but this does not take effect or, worse, aggravates his illness; In addition to representing an expense, it will generate a psychological impact on the patient and his family. What can it mean for the patient? Definitely, the first thing that comes to mind may not be to doubt the treatment, but in the severity of the disease and, therefore, lose hope. Now imagine that our child presents an infectious process of bacterial origin, which is treated with an antibiotic that does not contain the amount of active ingredient according to technical specifications or, what is worse, that contains more of the active ingredient and represents a risk of toxicity in the patient because it contains toxic chemical components for the body(3). Definitely, the infectious process could worsen and generate greater hospital stay

Current leader of the International Pharmacovigilance Consultancy Vigilantia Healthcare and pharmaceutical teacher at Educational Institution in Peru.

or cause other health problems in the patient. This situation generates a lack of confidence not only in medicines but also in health professionals, in the health system, and in governments, who attest to these medicines circulating in the market, opting for other alternative treatment measures that are not always safe or scientifically investigated.

This situation is not limited to the most expensive drugs or the best-known brands, but also affects generic and patented products to an equal extent(4). It is well known that generic drugs must also demonstrate bioequivalence. In many Latin American countries, there is a great difference in efficacy between a branded drug and a generic drug of the same active, for example, a study conducted in Mexico revealed that a generic corticosteroid did not reach the expected efficacy compared to other products, so generic substitution could show a lower clinical response than that of the original brand(5). There are regulatory advances in relation to the presentation of bioequivalence studies of the registrations of certain molecules by the pharmaceutical industry, however, it is the patients who must communicate the lack of efficacy or nonoptimal clinical responses with these products.

Medical products of lower or substandard quality identified with high frequency have corresponded to all categories, in particular drugs, vaccines, and in vitro diagnostics, however, the most reported are antimalarials and antibiotics(7). On the other hand, the main safety problems that have been reported with the use of substandard quality medicines are bacterial resistance, higher prevalence of diseases, hospital readmissions, overdose, misdiagnosis of communicable diseases that put public health at risk, for example, COVID-19, or poisoning due to high levels of active ingredient in products.

The WHO issued an alert in December 2022 on the detection of a product containing methotrexate (a product that belongs to the WHO list of essential medicines for its indications in cancer and autoimmune diseases) contaminated with Pseudomonas aeruginosa, which represents a high risk, given that bloodstream infection by Pseudomonas aeruginosa it is serious and can cause death. The important finding to note is that adverse events were detected in pediatric patients.

Another alert recently issued by WHO in December 2022 regarding substandard quality medical products concerns products in syrup presentation that contained unacceptable amounts of diethylene glycol and/or ethylene glycol as contaminants. These agents pose a great danger since toxic effects can include abdominal pain, vomiting, diarrhea, inability to urinate, headache, altered mental status, and acute kidney damage that can lead to death.

Having substandard medical products represents a significant public health challenge that we all face, for which global authorities and organizations must take action. With this situation, the importance of having robust pharmacovigilance systems that allow addressing and prioritizing care in the post-authorization surveillance of medical products is reinforced.

The healthcare professionals involved must ensure that the drug supply chain is carried out with ethics, professionalism, and integrity so that in this way it is guaranteed that the quality control and safety of the entire process comply with regulatory and quality requirements. It is recommended to reinforce community action on the part of health professionals to educate patients to identify and report in a timely manner any suspected adverse reaction with the use of all medical products, only in this way, we can analyze and investigate the origin of substandard quality products and with these reports generate concerns and investigations by the authorities for the issuance of more safety alerts.

The authorities play an important role in stopping and controlling the entry and circulation in the market of medical products that do not demonstrate quality, efficacy, and safety. The rigor in the request of controls and minimization of risks to manufacturers can contribute to reducing this problem, in addition to the stimulation of reports by all actors in the Health and Pharmacovigilance Systems with research actions and even withdrawal of unsafe medical products of poor quality.

References

OMS. 1in10medicalproductsindevelopingcountriesissubstandardor falsified.Available in: https://www.who.int/en/news-room/detail/28-11-20171-in-10-medical-products-in-developing-countries-is-substandard-or-falsified OMS. Productosmédicosdecalidadsubestándaryfalsificados, Available in: https://www.who.int/es/news-room/fact-sheets/detail/ substandard-and-falsified-medical-products

Productosmédicosdecalidadsubestándaryfalsificados,el crecientedesafíoparalasaludpública. Ángel Luis Jiménez. Consalud.es, September 4, 2022. Available in: https://www.consalud.es/industria/ datos-medicamentos-falsificados_118555_102.html

DeclaracióndelaAMMsobreasegurarladisponibilidad,calidady seguridaddelosmedicamentosenelmundo.Adopted by the 72nd WMA General Assembly (online), London, United Kingdom, October 2021. Available at: https://www.wma.net/es/policies-post/declaracion-de-la-amm-sobre-asegurar-ladisponibilidad-calidad-y-seguridad-de-los-medicamentos-en-el-mundo/ Juan Pablo Castanedo-Cázares,* Judith Quistián-Hemández,* Bertha Torres-Alvarez,* Antonio Torres-Ruvalcaba,** Benjamín Moncada,** Estudio del efecto antiinflamatorio de un corticosteroide tópico: marca reconocida versus genéricos. GacMédMéx, Vol. 137 No. 4, 2001. Medicamento. Disponible en: https://www.cancer.gov/espanol/publicaciones/ diccionarios/diccionario-cancer/def/medicamento

Productosmédicosdecalidadsubestándaryfalsificados. International Council of Nurses position statement. Available at: https:// www.icn.ch/sites/default/files/inline-files/PS_E_Substandard_and_ Falsified_Medical_Products_es_0.pdf

Alerta de Producto Médico N°8/2022: Subestándar (contaminado) METHOTREX 50mg identificado en la región del Mediterráneo Oriental de la OMS. December 27, 2022.

Alerta de Producto Médico N°1/2023: Medicamentos de dosificación líquida subestándar (contaminados) identificados en la Región Europea de la OMS. January 11, 2023.

Casa Ipomea Sayulita, Jalisco.

PREDICTIVE ANALYTICS IN PHARMACOVIGILANCE

consultant and expert

Dr. Siva Kumar BUDDHA

Pharmacovigilance

Predictive analysis is a statistical technique that uses historical data to identify patterns and make predictions about future events. In the field of pharmacovigilance, predictive analysis is used to identify potential safety concerns associated with a particular drug or class of drugs.

One common use of predictive analysis in pharmacovigilance is in the detection of adverse drug reactions (ADRs). By analyzing large amounts of data from clinical trials and post-market surveillance, researchers can identify patterns of ADRs that may not have been previously recognized. This can help to identify drugs that may be more likely to cause certain types of ADRs, and can also help to identify patient populations that may be at increased risk.

Another common use of predictive analysis in pharmacovigilance is in the identification of potential drug interactions. By analyzing data on the use of multiple drugs in combination, researchers can identify patterns of drug interactions that may not have been previously recognized. This can help to identify potential drug interactions that may be more likely to occur, and can also help to identify patient populations that may be at increased risk.

Predictive analysis can also be used to identify potential risk factors for drug-induced liver injury. By analyzing large amounts of data on liver function test results, researchers can identify patterns of liver injury that may not have been previously recognized. This can help to identify drugs that may be more likely to cause liver injury, and can also help to identify patient populations that may be at increased risk.

Predictive analysis can also be used to identify potential risk factors for medication errors. By analyzing large amounts of data on medication errors, researchers can identify patterns of medication errors that may not have been previously recognized. This can help to identify factors that may be associated with increased risk of medication errors, and can also help to identify patient populations that may be at increased risk.

In summary, predictive analysis is an important tool in pharmacovigilance, helping to identify potential safety concerns associated with drugs, identify patterns of ADRs, drug interactions, druginduced liver injury and medication errors, and identify patient populations that may be at increased risk. This can lead to better-informed decisions and improved patient outcomes.

The most counterfeited drug groups in the world

1. Genitourinary system medications and sex hormones

According to INTERPOL, counterfeit or unauthorized erectile dysfunction drugs accounted for approximately 40% of all products seized in 2022, following a global operation in 94 countries called “Pangaea XV”(1). These products, in addition to not complying with formal sanitary requirements (such as carrying the legend of the route of administration, for example), become poisonous and even deadly. One of the main causes of the massive counterfeiting of this drug is its great informal demand through the internet. Many people avoid visiting their doctors due to the shyness that such diseases can generate, so they go to online pharmacies or fraudulent distributors without regulation where they are not required to present a prescription.

2. Central Nervous System Drugs

Also known as Central Nervous System depressants, such drugs are made up of sedatives, tranquilizers, and hypnotic medications, such as muscle relaxants and anxiolytic medications. These drugs are designed to encourage neural processes, so they are used to treat anxiety, panic, stress reactions, and sleep disorders. According to the WHO, millions of people around the world suffer from a neurological disorder, for this reason, the high demand for drugs to combat such diseases has led to their illegal manufacture on a large scale.

3. Anti-infectives

These drugs include the categories of antibacterial, antifungal, antiviral, and antiparasitic. One of the biggest problems faced by the counterfeiting of this type of medicine is that it promotes antibacterial resistance, which, according to WHO data, by 2050 will be responsible for 10 million deaths per year in the world(2). In addition, counterfeit anti-infective medicines may be contaminated with heavy metals or other life-threatening materials.

4. Anticancer drugs

The counterfeiting of prescription drugs as cancer treatments has increased in recent years around the world; adulterated batches have been reported indicated to treat carcinomas, melanomas, lung cancer, breast cancer, among others. Among the most striking cases in the history of counterfeiting is the case of a man in China who collected empty containers of a cancer drug from hospital trash and refilled them with a solution of water and a variety of chemicals. These contaminated products were then shipped via the Middle East or North Africa to be sold to a European supply company(3).

5. Cardiovascular medications

Acetylsalicylic acid, popularly known as aspirin, is the most widely used drug not only for the prevention of myocardial infarction but also for its treatment since it reduces mortality if administered early during a heart attack(4). In general terms, counterfeiting of this and many other medicines occurs more frequently in developing countries because there is no effective sanitary regulation in manufacturing, transport, and storage. According to the Pan American Health Organization, cardiovascular diseases are the deadliest in the world, claiming 17.3 million lives annually. It is estimated that by 2030 almost 23.6 million people may die from one of these conditions(5).

Clinical Research Insider Editorial

References

INTERPOL (July 20, 2022), $11millioninillegaldrugsseizedafterglobalINTERPOLoperation. (Accessed 30 January 2023). Retrieved from: https:// www.interpol.int/es/Noticias-y-acontecimientos/Noticias/2022/11-millones-de-dolares-en-medicamentos-ilegales-incautados-tras-una-operacionmundial-de-INTERPOL

Rodriguez, H., National Geographic (Updated April 03, 2022). By2050antibioticresistancewillberesponsiblefor10milliondeathsannually.Accessed January 30, 2023). Retrieved from: https://www.nationalgeographic.com.es/ciencia/2050-resistencia-a-antibioticos-sera-responsable-10-millones-muertesanuales_18090

Campbell, A. Pharma (April 7, 2016). Dangersofdrugimportation:Acaseofcounterfeitcancerdrugs. Accessed January 30, 2023). Retrieved from: https://catalyst.phrma.org/dangers-of-drug-importation-a-case-of-counterfeit-cancer-drugs

Spanish Heart Foundation, Antiaggregants . Accessed January 30, 2023). Retrieved from: https://fundaciondelcorazon.com/informacion-parapacientes/tratamientos/antiagregantes.html

Pan American Health Organization. World Heart Day: Cardiovascular diseases cause 1.9 million deaths per year in the Americas. Accessed January 30, 2023). Retrieved from: https://www3.paho.org/hq/index.php?option=com_content&view=article&id=7257:2012-dia-mundial-corazon-enfermedadescardiovasculares-causan-1-9-millones-muertes-ano-americas

Dr. Carmen de la

Rocha,

Anti-obesity drug Semaglutide Approved by FDA After Demonstrating Efficacy in Teens

On December 23, the Danish pharmaceutical company Novo Nordisk published in a press release that its drug Wegovy® (semaglutide) has been approved by the US Food and Drug Administration (FDA) for the treatment of obesity in adolescents over 12 years of age. The drug had been approved for adults in 2021 and in 2017 for diabetes management.

Semaglutide works by mimicking the hormone called peptide, similar to glucagon-1 (GLP-1), which acts in the brain in areas that regulate appetite and food intake.

The results of the study that showed efficacy in adolescents have recently been published in the prestigious New England Journal of Medicine; the study included 201 participants over the age of 12, who showed a 16% decrease in body mass index in the group that received the asset compared to an increase of 0.6% in those who received placebo.

The prevalence of obesity in children and adolescents reported from 2007 to 2020 by the CDC is 14.7 million in the United States, and Novo Nordisk is committed to ensuring doses of the drug are available as soon as possible.

Novo Nordisk is a health industry in the biotechnology sector founded in 1923 based in Denmark, has more than 52,600 full-time employees, its shares closed on December 23, 2022 at $ 134, $ 27 more than the same day in 2021.

Childhood Obesity Facts, Overweight & Obesity, CDC. (Accessed: January 10, 2023). Available at: https://www.cdc.gov/obesity/data/childhood.html

Novo Nordisk; Press release (Dec., 2022). FDA approves once-weekly Wegovy® injection for the treatment of obesity in teens aged 12 years and older. (Accessed: January 10, 2023). [Press Release] Available at: https://www.novonordisk-us.com/media/news-archive/news-details.html?id=151389

Novo Nordisk A/S company Profile & Facts (2023) (Accessed: January 10, 2023). Available at: https://finance.yahoo.com/quote/NVO/profile?p=NVO

Weghuber, D., et al. (2022). Once-Weekly Semaglutide in Adolescents with Obesity. The New Englandjournalofmedicine,387(24), 2245–2257. (Accessed: January 10, 2023). Available at: https://doi. org/10.1056/NEJMoa2208601

Director of Research and Development at Drox Health Science. PhD in Biotechnology, Master in Biochemical Engineering. Member of the National System of Researchers level I.

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Sources

Drug to be tested in humans to treat obesity and diabetes

The Uruguayan-Argentine company Eolo Pharma, founded in 2018 by researchers from the Pasteur Institute of Montevideo and the University of the Republic, obtained approval from the Australian regulatory agency TGA to start the first human clinical trial of its compound MVD-1, developed for the prevention and treatment of obesity and its metabolic complications such as type 2 diabetes. MVD-1 works as an anti-inflammatory on adipose tissue (body fat) producing thermogenesis, known as the ability to generate heat in the body due to metabolic reactions, therefore, its activation involves the consumption of large amounts of glucose and lipids. In other words, the drug prevents the formation of fat deposits in the body, which outlines it as an excellent candidate for the prevention of obesity, mainly, as well as cardiometabolic and cardiovascular diseases.

In preclinical studies with mice, they have reported that during the first fifteen days of application the drug kept weight, glycemia and blood lipids stable, so the researchers expect optimistic results from clinical trials outlined for 2023 in Australia. The study will consist of a first phase to evaluate safety and efficacy, subdivided into two groups of 24 healthy participants, and a second phase with patients with overweight, obesity and impaired fasting glycemia; the patient recruitment period

Writing by

is expected to begin in January 2023 and the trial is scheduled to run during the rest of the year. It is projected that by the first quarter of 2024, once the first phase of the study is about to be concluded, the production and commercialization of the drug will begin.

Derived from the encouraging results obtained from preclinical trials aligned with regulatory requirements for safety, efficacy and toxicity in vitro and in animals, the pharmaceutical company managed to close a new round of investment for 3 million dollars. This second phase of investment involved the Argentine venture capital fund CITES, which had previously invested in the company, as well as international investors such as FICUS Advisory and Securitas Bioscience. With this new round, Eolo Pharma adds about 7 million dollars of investment in its research and plans a partnership with a pharmaceutical company or a venture capital firm to finance phase II clinical trials.

Abbreviation:

TGA: Therapeutic Goods Administration

Angosto, M. C. (2016, March). Termogénesis. In Anales de la Real Academia de DoctoresdeEspaña(Vol. 1, No. 1).

Dapueto, R., Rodriguez-Duarte, J., Galliussi, G., Kamaid, A., Bresque, M., Batthyány, C., & Escande, C. (2021). A novel nitroalkene vitamin E analogue inhibits the NLRP3 inflammasome and protects against inflammation and glucose intolerance triggered by obesity. RedoxBiology,39, 101833.

Ugueto, L. C. (December 23, 2022). El laboratorio uruguayo Eolo Pharma cerró una nueva ronda de inversión por US$ 3 millones. AméricaRetail. (consultation date: January 11, 2023). Retrieved from: https://www.america-retail.com/uruguay/el-laboratoriouruguayo-eolo-pharma-cerro-una-nueva-ronda-de-inversion-por-us-3-millones/. Prieto, A. (02 enero 2023). La uruguayo-argentina Eolo Pharma probará en humanos fármaco contra obesidad. SWI swissinfo.ch. (consultation date: 02 January 2023). Retrieved from: https://www.swissinfo.ch/spa/uruguay-ciencia_la-uruguayo-argentinaeolo-pharma-probar%C3%A1-en-humanos-f%C3%A1rmaco-contra-obesidad/48175512

Research and Development Analyst at Drox Health Science. PhD in Innovation in Medical and Pharmaceutical Biotechnology. Master in Molecular Biology.

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Dr. Wendy López Romero,

Writing by

Dr. Claudia Mejía Morales, Research and Development Analyst at Drox Health Science.

Moderna-Merck Alliance: Together for a Skin Cancer Vaccine

On December 13, 2022, the shares of the pharmaceutical company Moderna increased by 8% after the announcement of the results obtained in the phase 2 study (NCT03897881). This study involved the combination of the mRNA-4157 vaccine produced by Moderna plus the immunotherapy drug Pembrolizumab (V940) from Merck versus pembrolizumab alone. The synergy between both drugs (mRNA-4157/V940) led to a 44% decrease in skin cancer cases and a statistically significant improvement in recurrence-free survival (RFS) in patients with complete resection of stage III/IV cutaneous melanoma.

The strategic collaboration was agreed since 2016 in an agreement where Merck made an advance payment to Moderna of 250 million dollars so that the latter will use it to lead all research and development efforts in favor of the vaccine, Keytruda (pembrolizumab), the successful immune-boosting drug approved for nearly 18 types of cancer, is projected to be one of the world’s best-selling drugs

by 2023, adding nearly $3 billion in sales to date and is forecast to generate nearly ~$24 billion in sales by 2023. We hope that this new year will continue the studies that support the safety and efficacy of this innovative vaccine that represents hope in the fight against skin cancer.

Moderna - News Details: Merck and Moderna Announce strategic collaboration to advance novel mRNA-based personalized cancer vaccines with Keytruda® (Pembrolizumab) for the treatment of multiple types of cancer. JUNE, 29, 2016 Urquhart, L. The biggest-selling drugs of 2023. Evaluate Vantage®. Retrieved January 5, 2023: https://www.evaluate.com/vantage/articles/analysis/biggest-sellingdrugs-2023

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ThePhysician(1653)

Gerrit Dou (1613 - 1675)

Original title: ThePhysician

During the Middle Ages, the Renaissance and the Baroque, uroscopy was the method par excellence to detect internal diseases in patients. The diagnosis was carried out mainly through a visual inspection of urine. As shown in the work, urine was poured into a glass jar called a matula. The analysis included an examination of the color, sediment, and density of the liquid, however, records show that doctors also smelled and even tested the sample for acidity.

Oil on oak panel, 49.3 × 36.7 cm. At the Museum of Art History in Vienna.

González H. (2017): “Uroscopia”, Digital database of medieval iconography. Complutense University of Madrid. Online: www.ucm.es/bdiconografiamedieval/uroscopia

Source

Rogelio Marín

Mexico, spearhead of the scientific economy in Latin America

1. What is the objective of the Rómpela a la mexicana project?

The project was born with a concern, in the first instance, to return to my country what was offered to me at the time and, in turn, try to enable something else, that I did not find at that time. I started entrepreneurship at the age of 21; in the process, I found a very important gap of support for scientists or researchers who wanted to undertake projects and who for one reason or another, although they tried, did not find the spaces or the ways to do it. I realized that there were many factors in the different circles that surround entrepreneurship, so I set out to explore the whys to help the realization of the projects, as a way to give back what was offered to me.

Along the way what I built was a purpose; what I have learned over 30 years is that it costs the same effort to do something small as to do something very big, so I set out to do something to transform the economy and the economic model of our country, aligned with the theme of an economy based on knowledge, scientific research and technological development. And for that purpose, we built our objectives. The concept of Rómpela a la Mexicana arose from the idea that we always end up “breaking” it with an initial and impetuous effort, but along the way, for some reason, that effort is diluted; we are very good at helping in times of crisis but when we have to do it sustainably or constantly, something happens to us along the way, and this happens in many areas, such as football, business, family, and so on.

Mentor, Angel Investor and Orchestrator of 100% Mexican scientific and technological-based ventures. Telecommunications and Electronics Engineer, graduated from the National Polytechnic Institute; business consultant for 30 years and founder of the movement from Rómpela a la Mexicana.

Movement that disseminates and enables Mexican scientific and technological entrepreneurship.

The purpose of Rómpela a la mexicana is the transformation of our economic model and among our objectives is to build by 2025 at least 10 success stories of scientific entrepreneurship that are inserted in the market, either nationally or globally, and by 2030 to have at least one scientific-technological based company valued at one billion dollars.

The concept of unicorns has been heard a lot in the field of entrepreneurship, in fact we have several in Mexico, such as Bitso, Kavak, some Fintech, but we do not hear anything from science-based companies, which undoubtedly exist.

2. What are the keys to achieving commercial success in scientific entrepreneurship?

Our own experience and that of many colleagues who are involved in the subject of entrepreneurship tells us that there are two major profiles: the scientific entrepreneur or the scientist per se, who has the philosophy of “first I think, then I exist and then I do”, and the

traditional entrepreneur, who thinks “first I do it and then I think”, that is, first I throw myself and on the fly I compose. Our Latino culture works like this, we use a lot of effort, impetus and desire to get ahead in the beginning.

We give as an example the traditional entrepreneur, responsible for these constructions valued at a lot of money known as unicorns, which are few in Mexico (we have eight only for now), but we have family businesses of great ancestry that are surely well known, such as Bimbo, Femsa, and so many other family businesses that have evolved over the years and that have this profile, that is, they launch and see how they get ahead. The scientist, on the other hand, has another profile, but not because it is different means that he cannot do it, you simply have to focus the effort. So, what we have to do is enable the scientist to the elements so that “first I think then I am” is very fast and we are not in the famous saying that “too much analysis generates paralysis”, in other words, yes you have to analyze things through hard data, but you do not have to wait too long, and less today with so much technology and so many enablers.

Currently, human health has benefited from many accelerators at the scientific level, because before there were tests and too many internal processes to get a vaccine or an antibiotic; now there are even regulations that allow you not even to test on animals but through a computer or digital tests. Time has thus been shortened; obviously, the times of Nature are not the same as ours, but we can help, that is the big difference to being able to make a scientific venture can be close enough to a traditional venture that is successful. For this, we have to make a change of mentality in the scientist so that finally his entrepreneurship transcends.

3. You recently mentioned the knowledge-based economy, in broad strokes, what does it

mean and why is it essential to start applying it?

The general concept of the knowledge-based economy has to do with how to build economy, wealth, abundance or economic stability in a country or a region from science, research and formal knowledge; there is ample evidence that countries that base their economy on it have greater resistance and resilience to economic crises, now we saw it in the pandemic. Such countries evolve to their generations, not only repeat cycles or mistakes; knowledge is not only represented by the scientific and technological sector, but also by the learning of the past, of history in order to evolve and build the future based on knowledge and the maturity that knowledge allows.

4. What is your method of supporting entrepreneurship and investment in science and technology?

The first thing we do is work with the scientist, identify the one who wants to undertake, and start involving him in the field of entrepreneurship. It is not a matter of turning his back and putting him in courses, no, we are going to jump into the pool together and take him to the arena of entrepreneurship. In parallel we work with the industry; we have to let the national industry know that there is talent and that solutions can be developed to their needs, with some additional resources that surely today we do not have as available as other countries, such as our northern neighbors or China, so we must build that link and establish that an investment is not only the solution to an industrial need but also

the transformation of a national economy. In the same way, we have to link the other extremely important component which is investment. Both investment funds, angel investors and entrepreneurs themselves have to bet on you; just as they bet on investment from a digital financial company, or a car marketplace, they should also understand why it is important to invest in a scientific venture. The great challenge is that the investor bets on the entrepreneur, not necessarily on the project.

5. What are the strengths of Latin America for the development of scientific projects?

DDefinitely, the greatest strength we have as a nation is talent. The issue of talent drain has two approaches: that talent that does not find the space or fertile land to develop and goes to another country, and probably stays there, and the talent that ends up being employed in a place

where it knows that it will be able to do what it likes, which is pure research. But it will give the benefit to others. We believe on the other hand that there is a third reality, and it is the talent that is in Mexico or that even goes to another country, but from its trench can contribute to building scientific entrepreneurship in Mexico. After the pandemic, what we saw was a capacity for unity between scientists and researchers, especially young people, to create community and to feel united and not unprotected. There were a lot of dynamics and they started to build things from scratch, as well as the purpose of building something for the benefit of our country.

For us these are the engines of the movement and such circumstances should not be wasted; someone must do something because if the same thing is not going to happen as always, the efforts are going to be diluted and the young people are going to end up as usual, leaving the country or doing extraordinary things for others, or they stay here at the desk, which is not bad because pure scientific research must continue to exist, but we believe that those kids who bring the seed of wanting to

do something more, of doing entrepreneurship, we should not leave them alone and we should help them. Speaking of the amount available to invest in ventures, in recent years about 15 billion dollars have been made available for investments, not only scientific; only last year the investment ended in about 8 billion dollars at the Latin American level and for this year there will be another one more similar, so we are in the eye of the hurricane, in the eye of investments as a country and as a region, and a piece must be destined to the scientific sector.

Our goal is to put scientific entrepreneurship in the spotlight of the different actors so that they realize that it can be done and decide to invest in these projects. In the end, when you do scientific research, even if it’s for commercialization, you know that the impact is going to be global. For example, if we find a way to make clinical trials more accessible, or that

you do not have to leave home now with so much technology, or if we find a way to identify cervical cancer more quickly or effectively, the benefit is global because tomorrow it will be replicated around the world. And the goal is that, that it exists for everyone and that it is accessible because science allows it.

Rómpela a la Mexicana is a movement that we want to encompass all Mexicans both inside and outside the country, and these scientists who have this need to know that there is a space that can receive them, that there is a network that will accompany them and help them and that together we can do more things than if we do it alone.

Official Website: rompela.mx Clinical Research Insider Edition

Dr. Ana

Villaseñor-Todd

Alcoholic hepatitis, the excessive insult and disinterest in our liver health

Every beginning of the year we travel to enjoy the low temperatures of the north of the country, scenarios covered in white. Sadly, nothing is forever. We find spectacular sunsets and the wonderful flora and fauna of the Sierra de Arteaga. But there was no snow anywhere. The solemn meeting and disappointment of the little ones was cushioned by the company of pleasant friends. Once installed in a comfortable cabin we lit the fireplace while advancing the starry evening at the top of the forest: Alejandro Flores in a serious and shocking tone said: “I do not augur a good summer.” To which I immediately asked: Why such an optimistic comment? He went on to explain the following:

Fred Pierce published in 2006 the book When the rivers run dry: water – the defining crisis of the twenty-first century. The very structure of the book is a path to a deeper understanding “of the water problem,” which in much more systemic terms, says: “When rivers dry up: I) crops fail, II) we mine our children’s water, III) wetlands die, IV) floods may not be far away, V) engineers pour concrete, VI) men go to war for water and VII) civilizations

fail... dystopian panorama very popularized by movies like Mad Max... However, he also talks about how when the rivers dry up: VIII) we go to look for new water, IX) we try to catch the rain and X) we go with the flow.

Water management is a complex issue (and technically a system), one of those known as “wicked problems” since it has an impact on all aspects of life (ergo complexity). A lack, then, is the effect of a series of causalities. For example, some finds found from southeastern Baja California Sur may illustrate “the roots”:

1) More water use rights have been granted than is available (increasing the deficit).

2) In 20 years, we will need at least 46% more water than we have (increasing the load on the system).

3) The majority of the population does not know the quality of wells and water sources in their region (lack of information).

Scientist, doctor by profession and Mexican businesswoman noted for her studies in minimal hepatic encephalopathy, oxidative stress, quality of life and social cognition. Certified by the Pan American Health Organization (PAHO) as a facilitator of MhGap; CEO VICOMMA Group.

Technical committee: Alejandro Flores Márquez Systemic and strategic thinker with experience in sustainability, social change and conservation for the development and strengthening of local communities as a way to leverage environmental and lasting change.

“Life, although it may only be an accumulation of anguish, is dear to me, and I will defend it.”

-Frankenstein

4) There are different ways to get more water, we must evaluate its economic, social, and environmental advantages and disadvantages (there is no generalized solution).

5) Accelerated growth has been observed in the Eastern Cape (BCS), so more studies and information are needed to plan for the future and prevent a water crisis.

Looking at it that way, the right question is what do we use water for? Flushing a toilet consumes between 7.5 and 26.5 liters of water. In our civilization we do not use water correctly. So many liters of common and clean water to discard approximately between 300 and 450 ml of urine in a urination. Last summer the sultan of the north was scarred because we faced an unprecedented water crisis. Some companies donated 7.5 million cans of water, equivalent to two and a half million liters of the liquid and were distributed in the communities most affected by the water crisis. However, it is here that the judgment of humanity is questioned.

When we define our priorities, making decisions is extremely simple. The problem is who defines those priorities. To give an example: historically

alcohol consumption has been a part of human culture. Alcohol has been consumed as part of religious rituals and rites, but also as a safe, nutritious and healthy drink, as it has antimicrobial properties and contains calories. However, alcohol is a toxic substance; it is not produced by the body and is poisonous in high concentrations. Alcohol consumption levels and patterns of alcohol consumption are associated with chronic diseases. In general, light and moderate alcohol consumption (up to 14 g per day for women and up to 28 g per day for men) may be associated with a lower risk of mortality, mainly due to reduced risks of cardiovascular disease and type 2 diabetes.

Alcohol consumption dates back to our primate ancestors. In Greece, in the city of Hierakonpolis, is where the ruins contain evidence of the oldest brewery in the world dating back to 3400 BC. In Athens, the consumption of wine was considered a civic duty almost exactly as in our present age. The Romans were the next great drinking civilization to emerge in the classical world. When Dionysus’ followers arrived in Roman territory in the second century B.C., they were met with suspicion. People who congregated in large groups for the purpose of getting drunk made no sense to this sober society.

The Romans decided it was all part of a sinister plot to overthrow their rule; yes, from the Romans to the present day “Panem et circenses”.

In Christianity, wine could not only quench thirst and inspire joy, but it could also represent the proven blood of the son of God. The Crusades were a series of religious and political wars fought between Christians and Muslims for control of the Holy Land. When the Crusaders returned home, they were surrounded by unlimited opportunities to enjoy alcohol. Everyone in Europe drank and drank several times a day. Arnald de Villanova was a physician and alchemist who promoted the use of alcohol as a cure for any ailment. He believed that wine was suitable for all ages and blessed everyone in good health. He experimented with the science of distillation and called distilled spirits aqua vitae (water of life). Distillation first flourished in Germany, and, in the fifteenth century, apothecaries sold liquors to the public in gulps as a health tonic. In 1492, the Spanish kings, Ferdinand and Isabella, financed a fleet of ships that sailed across the Atlantic to the Americas. In 50 years, the Spanish conquered the Inca and Aztec civilizations and established an empire stretching from Florida to southern Chile.

Alcohol consumption peaked in the 1870s and then began a downward trend. As the world be-

came more industrialized, drunkenness was not compatible with a reliable workforce. Currently as in the Hellenic civilization alcohol consumption is everywhere, music concerts, football matches, birthdays, funerals, an entire industry around and no effort to avoid having a risky alcohol consumption. This idea doesn’t sell pleasure, I’m not going to write something ephemeral, these lines sell a long-term reward known as happiness.

Globally, half of deaths due to liver cirrhosis are alcohol-related. In Mexico, liver cirrhosis related to alcohol consumption also accounts for approximately 50% of the causes. This generates a public health problem that directly impacts high mortality and, as a consequence, high costs for the health system. Unlike other regions of the world, Mexicans have the highest alcohol consumption score and a high mortality rate from alcoholic liver disease with an intermediate category level of alcohol consumption per capita. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects (1).

It is well known that Mexico has the need to implement multisectoral interventions, strengthen psychosocial competencies to achieve the improvement of quality and access to mental health and addiction services. In Mexico, these

measures must be implemented from childhood. Patients with alcohol-related liver disease require comprehensive psychiatric evaluation and concomitant management by trained addiction personnel.

Alcoholic hepatitis (HA) is a frequent condition in the Mexican population, which is usually characterized by acute chronic liver failure (ACLF) for its acronym in English acute-on-chronic liver failure, important systemic inflammatory reaction and multiorgan failure, which in the severe variant of the disease implies a high mortality. The Mexican population has a mixed genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, the genes related to alcohol addiction can vary from one individual to another. In addition, they can be inherited as risk or risk-free haplogroups that confer susceptibility or resistance to alcohol addiction or alcohol abuse and possibly liver disease.

Alcohol-related liver disease (AHD) comprises varying degrees of injury ranging from simple steatosis to cirrhosis. Simple steatosis, initially macrovesicular and later mixed (macro and microvesicular), is the earliest change and is present in 90% of individuals who consume alcohol riskily; however, this injury is often reversible after abstinence. Although the prevalence of each histological lesion in AHD is not known exactly, it is estimated that 25% of patients with HD develop steatohepatitis and that about 15% progress to cirrhosis. The cumulative 5-year risk of developing hepatocarcinoma in patients with alcohol cirrhosis is estimated at 1%.

The quantification of alcohol consumption becomes relevant. The WHO, in its guidance on brief intervention to avoid risky alcohol consumption, defines a standard drink as 10 g of pure ethanol and recommends, for both men and women, not to exceed two standard drinks per day. The amount of

alcohol contained in a drink varies according to each continental region, and even differs in each country of the world. For the particular case of Mexico, the Official Mexican Standard (NOM) on “Alcoholic beverages. Sanitary specifications. Sanitary and commercial labeling”, published in the Official Gazette of the Federation (DOF) in March 2015, indicates that the approximate alcohol content in a “standard drink” is 13 g considering that its specific gravity is 0.785 g/mL.

The amount of alcohol consumed, regardless of the pattern of consumption, is the most important risk factor for developing AHD. Women are more susceptible to liver damage from alcohol than men. Some studies have even reported that women have a higher risk of suffering from HA by consuming half the dose of alcohol considered risky in men, likewise, women have a higher risk of accelerated progression of the disease and risk of developing cirrhosis vs. men. In patients with other diseases such as metabolic syndrome or chronic viral hepatitis by B virus or virus C, alcohol consumption, even in less than what is considered “risky consumption”, can favor and accelerate the progression of liver damage.

Hepatitis or steatohepatitis (AH) by alcohol has a large number of clinical manifestations ranging from asymptomatic state, with minimal symptoms or clinical signs of disease in its mild form, to a picture characterized by acute liver failure over chronic in its severe form. HA with a MELD (Model for End-Stage Liver Disease) score equal to or greater than 21 has an elevated risk of mortality at 3 months. The main causes of mortality at 90 days were: sepsis 20%, liver failure 24% and multiorgan failure 46%. In this same study it was shown that the amount of alcohol consumed has a negative impact on the survival of patients. Human malnutrition is another factor of poor prognosis. Diagnostic test for liver disease is liver biopsy and can be performed to establish the definitive diagnosis of liver disease related to alcohol consumption, to assess the exact

stage and prognosis of liver disease and to exclude additional or alternative causes of liver damage. However, due to being an invasive procedure is not recommended in all cases and the risk against the patient’s benefit should be evaluated individually.

Considering the history of risky alcohol consumption, bio-chemical alterations, together with the exclusion of chronic viral diseases such as hepatitis B or C, or autoimmune diseases, is usually sufficient to reach the diagnosis of cirrhosis due to EHA. Ultrasound, tomography and MRI can quantify steatosis and help exclude other causes of chronic liver damage, can recognize advanced stages of the disease (cirrhosis) and its complications.

Measurement of liver stiffness by elastography is useful for assessing liver fibrosis in alcohol-related liver disease. Among the radiological methods available to evaluate fibrosis, elastography has the highest validation for the detection of advanced fibrosis, and the best performance in ruling out the presence of cirrhosis compared to its performance in confirming the presence of cirrhosis.

Additional association studies will be required to establish novel strategies for the prevention, care, and treatment of liver disease in Mexico and worldwide. Patients with alcohol use disorder have a high prevalence of psychiatric comorbidity, especially anxiety disorders, affective disorders, psychosis, post-traumatic stress disorders, and schizophrenia. They may also have a history of sexual abuse, physical abuse, or social isolation. This may be a factor that will increase the risk of relapse into alcohol consumption.

This is why the consensus recommends a psychological and psychiatric evaluation, who should be responsible for the management of substance abuse, including alcohol. In addition, they are at high risk of developing other addictions, opioids, benzodiazepines and nicotine. The synergy of al-

cohol and tobacco use is established as a major risk for cardiovascular disease and cancer, including hepatocarcinoma. It is common for patients with chronic liver disease to lose withdrawal and cannot imagine how many times I have heard the phrase:

I will die of something, doctor ...”, my answer is always “Frankenstein said: I was wrong in only one thing: all the misfortunes I imagined and feared did not reach even the hundredth part of the anguish that fate had in store for me.

Laudanum was a medicine that bohemians consumed indiscriminately due to its narcotic properties. These properties were one of the factors that predisposed Mary Shelley to write the future of a patient with a risky consumption of alcohol through Frankenstein. Mary Shelley writes about Frankenstein as if speaking in her own flesh: I saw—with her eyes closed, but with keen mental vision—I saw the pale student of ungodly arts, kneeling beside the being she had assembled. I saw the horrendous ghost of a man lying down, and then, by some powerful ingenuity, I saw him manifest signs of life, and shake with clumsy and semi-vital movement.” It captures with perfect mastery over scientific morality, but also the pleasures of creation and destruction of life and the daring of humanity in its relationship with God.

Roman, S., Zepeda-Carrillo, E. A., Moreno-Luna, L. E., & Panduro, A. (2013). Alcoholism and liver disease in Mexico: genetic and environmental factors. WorldJournalofGastroenterology: WJG,19(44), 7972–7982. Retrieved from: https://doi.org/10.3748/wjg.v19.i44.7972

Khaderi, S. A. (2019). Introduction: Alcohol and alcoholism. Clinics in Liver Disease, 23(1), 1–10. Retrieved from: https://doi.org/10.1016/j.cld.2018.09.009

Velarde-Ruiz Velasco, J. A., Higuera-de la Tijera, M. F., Castro-Narro, G. E., ZamarripaDorsey, F., Abdo-Francis, J. M., Aiza Haddad, I., Aldana Ledesma, J. M., Bielsa-Fernández, M. V., Cerda-Reyes, E., Cisneros-Garza, L. E., Contreras-Omaña, R., Reyes-Dorantes, A., FernándezPérez, N. J., García-Jiménez, E. S., Icaza-Chávez, M. E., Kershenobich-Stalnikowitz, D., Lira-Pedrín, M. A., Moreno-Alcántar, R., Pérez-Hernández, J. L., Torre-Delgadillo, A. (2020). Consenso Mexicano de hepatitis alcohólica. RevistadeGastroenterologíadeMéxico(English Edition), 85(3), 332–353. Retrieved from: https://doi.org/10.1016/j.rgmx.2020.04.002

Rodríguez-Aguilar, E. F., García-Alanís, M., Pérez-Escobar, J., Sánchez-Herrera, D., Toapanta-Yanchapaxi, L., Ávila-Rojo, E., Visag-Castillo, V., & García-Juárez, I. (2022). Trasplante hepático en hepatitis alcohólica aguda: ¿debemos decir que no? Cirugía y Cirujanos, 90(5), 700–705.Retrieved from: https://doi.org/10.24875/CIRU.21000523

Shelley, M. (2012). Frankenstein. Penguin Classics.

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Irene Licona

and

In the framework of World Cancer Day 2023

Let’s talk about cancer... fearless

Myelofibrosis, How much do you know about this type of blood cancer?

More than three years after the COVID-19 pandemic (caused by the SARS-CoV-2 virus), much research has been done and continues to be done on this condition worldwide, especially on the sequelae that people who have already gone through the disease are presenting in the short, medium and long term. So many and indistinct that it seems that either we are getting used to it or we have stopped being afraid of the disease, especially now that it is not as lethal as at first.

It seems that fatigue, night sweats, bone, and joint pain are becoming part of our day-to-day to cope with them without the greatest problem, in the certainty that these symptoms, at least, will not kill us. However, there is no greater mistake – proven – than trusting or not giving importance to the “alarms” that the body is emitting through signs and symptoms, and that may well be the antecedent of something serious.

Did you know that if you feel pain or a feeling of fullness under your ribs on your left side, sweat at night, and constantly develop a fever, it could be an indication of a condition called myelofibrosis?

Myelofibrosis is a disease classified among hematological (blood) cancers that occur in bone marrow cells. It is a progressive condition that develops fibrous tissue that scars the bone marrow and has difficulty developing normal cells. It usually occurs in adults (over 60 years old), although currently a quarter of them are

Journalist

Communicologist graduated from UNAM. Columnist in Encuentro Vital; Science communicator specialized in Cancer.

under that age and there are even some cases in young people.

Identifying a condition such as myelofibrosis can be difficult, however, there are signs and symptoms that may occur more frequently in patients, including 14:

1. Splenomegaly. About 85% of people living with myelofibrosis have this symptom identified as an enlarged spleen.

2. Weight loss. Most blood diseases can have weight loss for no apparent reason.

3. Fatigue and weakness. The decrease in red blood cells by the bone marrow causes the person to live with chronic fatigue.

4. Bleeding or bruising. The unexplained appearance of bruises (hematoma) or bleeding for no reason is another symptom of the disease.

5. Bone or joint pain. Bone pain is a common symptom in people who start with the disease.

6. Excessive sweating. The presence of excessive sweating is a sign of affectation, especially at night.

7. Neutropenia. People living with this type of neoplasm are more susceptible to infections, this condition is known as neutropenia.

8. Pruritus. In addition to the presence of bruising or hematoma, itchy skin is common in people living with myelofibrosis.

9. Anemia. As a result of low red blood cell production, this condition develops.

10. Thrombocytopenia. This condition occurs due to the low concentration of platelets (thrombocytes).

11. Hepatomegaly. Enlargement of the liver is one of the manifestations that can appear in people living with this carcinoma.

12. Petechiae. It is the appearance of red, flat dots on the skin that are caused by bleeding.

13. Palido. Paleness of the skin may be a reflection of anemia, which is common in people living with this type of malignant tumor.

14. Fever. Some patients may experience lowgrade fever, as a symptom of myelofibrosis.

About one-third of people living with myelofibrosis have no symptoms, so myelofibrosis becomes mistaken for cirrhosis or severe anemia. It is a disease that can take six months to three years to be diagnosed; when it evolves, the patient is very clinically impaired when diagnosed. The correct way to identify it is to perform frequent medical check-ups and general studies on the patient who presents one or more initial symptoms.

Given the panorama described above, it is worth performing a bone marrow study if you suspect having some type of cancer in the blood, especially if you have a history of the disease in the family.

Bone marrow is a soft, spongy tissue with many blood vessels located in the center of most bones. The main function of bone marrow is to maintain a normal number of these three types of cells, replacing the old ones with new cells.

There are two types of bone marrow: yellow and red, the red contains stem cells that transform into red, white blood cells, and platelets; while yellow is composed of fat and stem cells that become cartilage, fat, or bone cells.

Blood cells begin as stem cells and subsequently develop into:

*Platelets: create plugs that stop bleeding in the area of an injury.

*Red blood cells: carry oxygen to the body’s tissues.

*White blood cells: fight infections in the body. They are divided into neutrophils, macrophages and lymphocytes.

Among the diseases that affect the bone marrow, we find anemia, leukemias, myelofibrosis, myelodysplastic syndromes and lymphomas. Bone marrow is analyzed through two main studies: bone marrow biopsy and aspiration, to look at cells and also genetic components.

1.- Bone marrow aspiration: procedure used to extract the liquid part of the bone marrow.

2.- Bone marrow biopsy: a procedure by which a small solid sample of the bone marrow is obtained.

Both studies are performed simultaneously and usually the sample is taken from the pelvic bone, located in the lower back on one side of the hip.

The essential for diagnosis is the bone marrow biopsy, where a small sample of bone tissue of 1 cm is taken to send to a hematopathology laboratory, and through it, the degree of fibrosis inside the marrow is identified. The hematologist is responsible for performing these procedures to examine the cells. The pathologist will be the specialist who will interpret the results to identify a disease such as myelofibrosis.

Is there a relationship between diet and oral health?

Introduction

Nutrition is the process by which human beings can get the nutrients they need in their day to day, but how does it all begin? We rarely ask that question, so it is important to know the role of the mouth at this stage since this is where feeding begins. Nutrition has been recognized as an essential component for the prevention of numerous chronic non-communicable diseases (NCDs) such as diabetes and hypertension, however, the impact it has on oral health as well as the prevention of major oral diseases has recently been studied.

Oral health

The main function of the mouth is to incorporate food into the digestive tract, which goes from digestion to absorption. Formed by the tongue and teeth, each with specific functions, such as the sense of taste and chewing for the formation of the food bolus. However, we cannot forget saliva, which plays a crucial role in food processing, lubrication, initiation of carbohydrate digestion with the enzyme amylase and control of oral infections.

Many oral conditions are preventable and treatable, however, the World Health Organization (WHO) in 2022, reported that, globally, about 3,500 million people suffer from some disease related to the oral cavity and that 3 out of 4 live in middle-income countries.

Main oral diseases

One of the most prevalent diseases around the world is tooth decay. Between 60 and 90% of school-age children are affected and almost 100%

of the adult population. This condition is caused by the accumulation of bacteria on the surface of the teeth converting simple sugars into acids, which subsequently destroy the tooth. A bad brushing technique, together with a diet rich in sugars can cause cavities, pain and, sometimes, tooth loss and infection.

On the other hand, there are diseases that affect the gum, called periodontal diseases, being the most common gingivitis and periodontitis, caused by genetic and environmental actors that are determinants in its development, however, there are other factors widely studied, smoking and the presence of diabetes being the main ones. In its most severe form (periodontitis) the gums can separate from the teeth and the supporting bone, which causes them to loosen and subsequently lose the tooth. It is estimated that periodontitis affects approximately 19% of adults, representing more than 1,000 million cases worldwide.

The role of diet in oral health

The diet of the human being varies according to his culture, religion and availability of food and preferences. Composed of three main macronutrients: proteins, lipids and carbohydrates, the latter is the one with the greatest presence in the human body, providing up to 60% of our diet, and acts as the main supplier of energy. Much

of it is found in foods such as fruits, dairy and vegetables, however, excess of these, particularly simple sugars, carries different types of risks and CNCDs, including those of the oral cavity. The National Health and Nutrition Examination Survey (NHANES), which included 2,437 young adults between the ages of 18 and 25, found that high sugar intake is associated with a high prevalence of periodontal conditions.

Depending on the type of carbohydrate consumed is the effect it can have on oral health. Excessive consumption of refined sugars promotes the imbalance between healthy and pathogenic bacteria that live in the oral cavity causing an inflammatory reaction, which leads to the appearance of this type of disease. A correct supply of micronutrients in the diet is important to maintain periodontal health and prevent its conditions. The antioxidant effects of certain vitamins such as A, C, E, folic acid and minerals such as calcium can have a positive effect on the prevention and treatment of periodontal diseases and, even, the deficiency of these is associated with their appearance.

Around the world, there are reports of vari-ous diets that have a positive impact on chronic diseases. The Mediterranean diet, the Okinawa diet, the Dietary Approaches to Stop Hypertension

(DASH) diet and the vegetarian diet are perfect examples to prevent diseases related to the oral cavity, as well as cardiovascular diseases, diabetes and cancer. While a Western diet, which is characterized by excessive consumption of ultra-processed foods, refined sugars and saturated fats, increases the risk of CNCD and periodontals.

A study developed by researchers at the University of Würzburg, in Germany, evaluated the effect of a lettuce juice containing 200 mg of dietary nitrate (a nitrogenous compound present in green leafy vegetables) on gingival inflammation of 44 patients with chronic gingivitis who received non-surgical periodontal therapy (first line of treatment). They found that the group with the juice consumption had a greater reduction in gum inflammation, along

with an increase in the number of good bacteria associated with oral health.

Conclusions

A correct diet characterized by a consumption rich in fruits and vegetables, as well as the correct contribution of vitamins and minerals can reduce inflammation of the gum, improve healing and reduce the number of teeth with bone loss, however, dental hygiene, as well as proper brushing are a fundamental part of the treatment of these diseases, therefore, balanced eating patterns rich in these compounds, together with correct professional advice to improve hygiene practices, could help for the prevention or treatment of oral diseases.

World Health Organization. WHO fact sheet on Oral Health. [Internet]. 2022 [cited 2023 Jan 23]. Available from: https://www.who.int/news-room/fact-sheets/detail/oral-health

Fiorillo L. Oral Health: The First Step to Well-Being. Medicina . 2019. 7;55(10):676.

Isola G. The impact of diet, nutrition and nutraceuticals on oral and periodontal health. Nutrients. 2020;12(9):1–6.

Dodington DW, Fritz PC, Sullivan PJ, Ward WE. Higher intakes of fruits and vegetables, β -carotene, vitamin C, β -tocopherol, EPA, and DHA are positively associated with periodontal healing after nonsurgical periodontal therapy in nonsmokers but not in smokers. JNutr.2015;145(11):2512–9.

Woelber JP, Bremer K, Vach K, König D, Hellwig E, Ratka-Krüger P, et al. An oral health optimized diet can reduce gingival and periodontal inflammation in humans - a randomized controlled pilot study. BMC Oral Health. 2016;17(1):1–8.

Martinon P, Fraticelli L, Giboreau A, Dussart C, Bourgeois D, Carrouel F. Nutrition as a Key Modifiable Factor for Periodontitis and Main Chronic Diseases. JClinMed.2021;10(197).

Jockel-Schneider Y, Goßner SK, Petersen N, Stölzel P, Hägele F, Schweiggert RM, et al. Stimulation of the nitrate-nitrite-NO-metabolism by repeated lettuce juice consumption decreases gingival inflammation in periodontal recall patients: A randomized, double-blinded, placebo-controlled clinical trial. JClinPeriodontol.2016;43(7):603–8.

Erick Manuel Rodríguez

Student of the Degree in Nutrition.

Miguel

Clinical Nutritionist. PhD student in Translational Nutrition Sciences. CUCS. UdeG. Professor of Subject, Universidad La Salle. Saltillo, Coahuila.

Carrera Quintanar

of the Food Science Laboratory. CUCS, UdeG. Member of the National System of Researchers level I.

Castro

CUCS, UdeG.

A. Robledo Valdez

Lucrecia Susana

Head

MEDICINAL CANNABIS REIMBURSED

In the 1970s, the British clinical epidemiologist Archie Cochrane, one of the pioneers of evidencebased medicine, defined three concepts related to decision-making when pondering a medical treatment: efficacy, effectiveness, and efficiency. Efficacy determines whether a treatment does more good than harm under controlled conditions, such as those of a clinical trial (can it work?). Effectiveness assesses whether a treatment does more good than harm when administered under normal conditions of healthcare practice (does it work in the real world?). Efficiency measures the effect of an intervention in relation to the resources it requires (is it worth it?).

To date, the clinical evidence about the efficacy of cannabis-based medicinal products (CBMPs) for the management of chronic conditions is still a subject of controversy. A systematic review of randomized controlled trials (RCTs) commissioned by the International Association of the Study of PAIN (IASP) concluded that RCTs in this field have a high risk of bias. It should be kept in mind that most of these trials were aimed at bringing to market two cannabis-based authorized medications, Sativex and Epidiolex,

and did not seek to characterize those in chronic pain populations but rather in multiple sclerosis and refractory pediatric epilepsy, respectively. However, a significant body of real-world evidence (RWE) obtained in countries where access to cannabis for therapeutic purposes is permitted is suggesting that chronic pain patients report robust improvements in their quality of life when CMBPs are added to their treatment regimen. Based on these findings and in contrast to the IASP position, the European Pain Federation recommends considering medical cannabis as a thirdline therapy for chronic neuropathic pain while, for all other cases of chronic pain, the use of CBMPs should be considered as an individual therapeutic trial. This means that, if approved treatments have failed, and after careful analysis and multidisciplinary assessment, physicians could prescribe medicinal cannabis to their patients if they consider that could represent a benefit.1

In 2022, several peer-reviewed publications reported on the effectiveness of CBMPs, including more than 15,000 patients from around the world taken collectively. Studies were performed in Israel,2 Australia,3 Colombia,4 Denmark,5 and the UK,6 and all of them showed similar results, which further help profile those patients that can benefit the most from adding medicinal cannabis to their therapeutic management, as well as relevant details in terms of dosing regimens and associated side effects to better inform medical practice and reassure prescribing physicians. We can only

Guillermo MorenoSanz

Global Scientific Director at Khiron Life Sciences Corp.

PhD.

wish that 2023 will be the year in which the third dimension, that of efficiency, will be tackled. Cannabis derivatives are typically approved only for patients that have trialed and failed other therapeutical options and are usually refractory to treatment. Still, the robust improvement in health-related quality of life reported by chronic patients in observational studies has been a decisive argument for different organizations to compel insurers into covering the cost of this therapeutic option based on quality-adjusted life years (QALYs) associated to CBMPs .7

As prominent examples, in the first weeks of 2023 the Colombian government stablished the mandatory coverage of CBMPs in the National Health Program and the UK’s National Health Service reimbursed for the first time the cost and clinical fees to a patient receiving treatment with CBMPs. Many experts have indicated already that insurance reimbursement represents the ultimate barrier for the actual implementation of cannabis-based treatments, thus protecting legitimate operators and expanding legal markets, such is the case of Germany in Europe and Colombia in Latin America, while increasing treatment adherence and preventing patients from falling back into the black market. Having a route for patient reimbursement for CBMPs is an important pillar of our global strategy at Khiron Life Sciences which we just finally achieved with mandatory reimbursement in Colombia. It would be, therefore, extremely important we start seeing welldesigned cost-benefit analysis being conducted in legal jurisdictions which can further reassure policy makers of the efficiency of CBMPs as an early therapeutic intervention.

epidemiológicas de la población de pacientes: A Prospective Study. Front.Med.9, (2022).

Vickery, A. W., Roth, S., Ernenwein, T., Kennedy, J. & Washer, P. A large Australian longitudinal cohort registry demonstrates sustained safety and efficacy of oral medicinal cannabis for at least two years. PLoSOne17, e0272241 (2022).

Moreno-Sanz, G. et al. Sex-Dependent Prescription Patterns and Clinical Outcomes Associated With the Use of Two Oral Cannabis Formulations in the Multimodal Management of Chronic Pain Patients in Colombia. Front.painRes . (Lausana, Suiza) 3, (2022).

Horsted, T., Hesthaven, K. L. & Leutscher, P. D. C. Safety and effectiveness of cannabinoids to Danish patients with treatment refractory chronic pain-A retrospective observational real-world study. Eur.J.Pain27, 234-247 (2023).

Moreno-Sanz, G., Madiedo, A., Lynskey, M. & Brown, M. R. D. ‘Flower Power’: Controlled Inhalation of THC-Predominant Cannabis Flos Improves Health-Related Quality of Life and Symptoms of Chronic Pain and Anxiety in Eligible UK Patients. Biomed.2022, Vol. 10, Página 2576 10, 2576 (2022).

Erku, D., Shrestha, S. & Scuffham, P. Cost-Effectiveness of Medicinal Cannabis for Management of Refractory Symptoms Associated With Chronic Conditions: A Systematic Review of Economic Evaluations. ValueHealth24, 1520-1530 (2021).

Eisenberg, E., Morlion, B., Brill, S. & Häuser, W. Cannabis medicinal para el dolor crónico: The bermuda triangle of low-quality studies, countless meta-analyses and conflicting recommendations. Eur. J. Pain (2022) doi:10.1002/EJP.1946.

2. Bar-Lev Schleider, L., Mechoulam, R., Sikorin, I., Naftali, T. & Novack, V. Adherencia, seguridad y eficacia del cannabis medicinal y características

Orozco Moreno

Art and technology: allies who cannot antagonize each other

Recently the internet went crazy with the reach of artificial intelligence; many people feel that we are closer to Futurama than ever. In various social networks, apps and pages went viral in which, through an AI, photos could be converted into creative designs of various types, from anime to images that seemed taken from a video game.

The issue generated controversy since people within graphic design argued that the abuse of this, or at least stopping using it in a merely playful way, that is, that people began to use it to create designs for professional or business purposes, could create a labor crisis for them. This discussion is not new, it has happened in music with autotune in singers since it is a tool with which (according to many defenders of singing) anyone can make an album even if they sing badly.

The question before all this is, then, is technology seriously so inimical to art and creative minds? Is true art only that which is made as a craft, bordering on the artisanal? If there is technology,

does it cease to be art? Given all this controversy that can make us fall into a very deep philosophical conflict, my opinion is that not to all those questions. There is technology that is a great ally of art and here I will show some gadgets that, well applied, can make music, design or architecture a more complete, aesthetic, and just as creative work as if the pure magic of the hands were used.

Music and dance are two artistic activities that invariably go hand in hand, and the Phonotonic is designed so that instead of creating a dance with

Communicator and Historian from the University of Guadalajara. Dedicated to journalism and content creation about technology, geek culture and video games on the internet.

Mauro

Courtesy: Photononic

music, music is composed with dance. These sensors are linked to any smart device in which music will be created, with your movements.

On the other hand, we have the Misa Digital Kitara, an electric guitar that, instead of strings, has a touch screen and touch sensors on the handle. The possibility of effects, audio editing, and production

with this guitar are enough for a creative mind to fly like never before with an ordinary guitar.

Finally, I will talk about art which is perhaps mo-re complex because of its brotherhood with disci-plines such as engineering: architecture. The Structure Sensor Pro is a camera that serves as a 3-dimensional sensor. It connects to a tablet or laptop and scans from a room to an entire building. This product is ideal for space remodeling or interior design, however, such technology was originally built for health care. According to the developers, the device was designed to be an auxiliary in demanding healthcare environments. With precision textured 3D scanning and industrial-grade calibration

capability, this device serves both to generate accurate images of the human body and to perfectly map a real estate structure. Thus, technology proves to be an ally that can be very close to art. The artist will never be at risk if he approaches the right technology, to print better and better what no AI can ever do: the personal stamp, the emotions, and the care that can be given to a creative product. Technology is also available for a more precise feeling.

Courtesy: Misa Digital Kitara

Courtesy: Structure Sensor Pro

Courtesy: STEPHANIE ARNETT / MIT TR, GETTY

Disruptive technology; from the digital age to the quantum age in 2023

New advances in technology have positioned quantum computing as the new promise to evolve the world economy, as it has the potential to revolutionize materials science, the pharmaceutical industry and virtually any field of knowledge, as it can solve problems that ordinary computers would take thousands of years.

So-called supercomputers are computers that take advantage of the nature of quantum mechanics (matter at the atomic level) to solve problems that are too complex that exceed the capacity of traditional computers. Such devices have positioned themselves as the development par excellence for the future, as quantum simulation can be applied to improve the processes of a myriad of fields. For example, in the field of communication,

such technology is expected to ensure the transfer of confidential information in a shielded manner, the exchange of securities between banks or the protection of digital assets; generally speaking, it is planned that everything will be shared using quantum technology in a few years. Other applications of quantum simulation would be aligning satellites more accurately, accurately recording magnetic fields or measuring brain waves.

In the same sense, one of the great advances will be in the area of scientific research and its relationship with manufacturing, because when scientists and engineers face very complex problems in their areas, they resort to supercomputers. Among the qualities of such devices is the performance of extremely difficult and time-consuming tasks; while an ordinary computer has a limit on its ability to process a significantly large amount of information, supercomputers, for their part, can analyze a large database of millions of components as a relatively easy task, such as protein sequences at the atomic level or data about the universe.

Quantum computers were designed to transform the way research is worked. Its scientific application within pharmaceutical companies and chemical industries means an impact on processes and expenses, since quantum simulation allows evaluating the properties of materials before sending them to the laboratory, thereby reducing the expenses of companies, in addition to helping in the search and choice of materials easier to recycle.

The goal of the pharmaceutical industry will be to produce more effective and cheaper drugs with the help of supercomputers to be developed within the next few years, because with their scope molecular structures could be

simulated in a quantum computer in a matter of seconds and calculate the composition of the active ingredients, thereby saving thousands of laboratory tests. It can be said that quantum computers offer a new set of tools to understand the universe and facilitate the life of the human being. Companies, investors, and researchers are increasingly investing in financing its development and implementation. It should be noted that the quantum computer will not replace the PC computer, but will complement it. For now, quantum computing is not a tool suitable for personal computers, but is limited to the corporate, scientific and technological world, due to its great complexity.

IBM, Tesla, Google, and Volkswagen are some of the companies already implementing quantum computing. However, it will be necessary to wait between 5 and 10 years before it can be used in practice, since it is still in the development phase. In this sense, the functionality of quantum computers is not only a matter of technology but of money, it costs between 3,000 dollars and The MIT Technology Review ensures that, although the market is highly competitive, from 2023 companies will begin to work collaboratively for long-term results, with important implications in biology and medicine.

Clinical Research Insider

Orígenes Romero Porras

Whathasnoname. A side effect

Piedad Bonett, Colombian author, narrates in Lo que no tiene nombre the story of Daniel, a young artist who threw himself from the fifth floor of a building in New York, on Saturday, May 14, 2011, at one and ten in the afternoon. Daniel was twenty-eight years old and had been studying for a master’s degree at Columbia University for ten months. His first surname was Segura and the second was Bonett.

Like the words “cancer” or “HIV” in Susan Sontag’s works, Bonett isn’t afraid to call the death of his own son suicide. As a poet, Bonett understands the relevance of the sensory: “Life is physical,” he says, as if avoiding metaphysical verbiage that fails to fill the void left by the death of a loved one. The author concludes that “in the face of the pain of the death of a son, all literary mystifications are meaningless.”

In the face of loss, the author, regardless of this literary metaphysics, focuses on the material: “true life is physical, and what death takes away is an unrepeatable body and face: the soul that is the body.” It crosses that terrain where idealism vanishes and flesh arises: “language refers us to a reality that the mind cannot comprehend.” The author passes through the sieve of paper that reality that, so atrocious, seems fiction. Bonett writes to bring his son back from dreams to carnal reality. Susan Sontag in Disease as a Metaphor

reflects on the vocabulary of war used to express the conditions in which people with cancer live, words like “struggle” or “combat” are nothing more than euphemisms that lead the patient to experience isolation.

Piedad Bonett writes from the experience of the condolences offered: “to say that he has already rested would be to incur a crude commonplace and a naivety that does not conform to reality. This one is much crueler: Daniel does not rest because he is not.”

If she writes only once about Daniel’s mental condition, it’s not out of fear. Daniel’s schizoaffective disorder is not Daniel. One is not their illness, for “there are no diseases but patients.” However, the author cannot get away from that war vocabulary that involves a Daniel who wanted to resist, who “carried for eight years a terrifying mental illness that turned his days into a painful and relentless battle.”

Daniel, his mother says, took acne pills for a while. After the suicide, Piedad Bonett researched about side effects. And yet, he does not blame the doctor or the treatment: “There is no point in rebuking anyone, there is no point in writing that letter that I have reviewed so many times mentally: my son has already died, with his skin intact.” b

Degree in History from the University of Guadalajara. Former Paralympic athlete (20062017). Interested in the relationship between art and history. Literary analyst.

But it cannot forbid itself to elaborate a hypothesis. At the age of nineteen, late acne appeared on Daniel’s face before which he was recommended “a highly dangerous drug, which puts the liver at risk and therefore forced him to periodic examinations.” And this is where there is finally a villain: the side effect.

Piedad Bonett’s research is terrifying: “That acne me-dication was already known about in 2001 but no one was careful to tell us that ‘cases of depression, psychotic symptoms and rarely suicide attempts have been reported.’” An exceptional case for medicine can be the entire life of a human being.

While it’s a possibility, Bonett isn’t sure: “I wonder what this could have been in Daniel’s case, and my intuition tells me, over and over again, that it was acne medication.” However, she is clear in respecting the fact as a decision of her son: two months after the suicide, the forensic analysis revealed that the boy had decided to stop psychiatric treatment for schizophrenia. It is her own research and the knowledge she has about her son that leads her to these reflections, not conclusions, because we are facing a chronicle about the suicide of a young artist

and in turn, an essay on this that Camus highlighted as the only truly serious problem in philosophy.

Bonett turns to a confession: “memory always lies” and that is why we are not properly facing a chronicle in real time, but facing the meditations that produced his own mourning. “The fact of having lived something, whatever it is, gives the imprescriptible right to write about it,” argues the Colombian. And I couldn’t write a fiction about her pain. He leaves us a beautiful phrase by way of apology: “The world has always laughed at the crazy. Of Don Quixote, although with a background of tenderness. Of Hamlet, not without some admiration. How could I, now, laugh at madness?” What has no name” is nothing more than an exercise to name.

Piedad Bonett delivers a creation that continues her son’s legacy along a special path, different from the path on which we group Shakespeare’s characters. “The pain seems, perhaps by compensatory law, to grant us rights,” says the author, for her and for us.

Thepharmacist(1714)

Frans van Mieris (1662 - 1747)

Original title: ThepharmacistorTheapothecary.

At the National Museum in Amsterdam, Netherlands.

In the Spain of Philip IV, in the year 1650, an order was issued for Pharmacy to be considered a Scientific Art in all its kingdoms, thereby endowing the same value as Medicine. In the work, we can see an apothecary elaborating what seems a formula, supported by a thick book that is probably a Pharmacopoeia. Also, you can perceive a kind of recipe that is on the table. Around it, you can see essential elements of every pharmacist such as mortar, aloe plant, the fruit of the Papaver somniferum, ceramic containers (albarelos) and a long-necked bottle (redoma).

Source Colegio Oficial de Farmacéuticos de Madrid. (30 Julio 2015). Cortesía: https://blog.cofm.es/farmaceutico-frans-van-mieris-esencia-profesion/