Biotechnological therapies and biosimilars for COVID-19: scarcities, poor regulation, and pharmaceutical black market: a case analysis in Ecuador

At the beginning of the COVID-19 pandemic, Ecuador was unprepared for the overwhelming number of COVID-19 cases. As the general population started to see the eff ects of the pandemic, unproven treatments and medications were sought by the population to try to ameliorate the impact of the pandemic. The growing demand for a cure, the fear of dying from COVID-19, and the lack of therapeutic rigour, pushed a signifi cant number of people to seek help outside the traditional healthcare system. Doctors, pharmacists, and patients started prescribing or selfmedicating pharmacological products that were later shown to be ineff ective, toxic or even contraindicated. In Ecuador, most people who developed the severe acute respiratory syndrome associated with infection by the coronavirus 2 (SARS-CoV-2) virus, which causes COVID-19, used antibiotics (azithromycin), antiparasitic medications (hydroxychloroquine or ivermectin), dangerous chemical products (chlorine dioxide) and in some cases, biological medicines, to try to cure or protect themselves from COVID-19. The growing demand for therapies that were unavailable, as well as the rise in misinformation, created the perfect scenario for the misuse of medicines and enabled the appearance of a rampant black market of unregistered biological products. In this manuscript, we describe the Ecuadorian experience in relation to the off -label use of biological and biosimilar products during the COVID-19 pandemic, the role of the pharmaceutical black market, and the lack of national regulations to avoid dangerous practices. To the best of our knowledge this is the fi rst report that has aimed to describe the unapproved and even illegal sale and use of biologicals, biosimilars and related products, with or without approved therapeutic indications in the treatment of COVID-19.

Download Full-text

The psychological impact of COVID-19 on the mental health in the general population

QJM ◽

10.1093/qjmed/hcaa201 ◽

2020 ◽

Vol 113 (8) ◽

pp. 531-537 ◽

Cited By ~ 32

Author(s):

G Serafini ◽

B Parmigiani ◽

A Amerio ◽

A Aguglia ◽

L Sher ◽

...

Keyword(s):

Mental Health ◽

Psychological Distress ◽

General Population ◽

Severe Acute Respiratory Syndrome ◽

Psychological Impact ◽

Psychological Reactions ◽

Chinese City ◽

Anxiety Depression ◽

The Impact

Abstract As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak. The role of risk and protective factors against the potential to develop psychiatric disorders in vulnerable individuals has been addressed as well. The main implications of the present findings have been discussed.

Download Full-text

A randomized phase II trial of oral vinorelbine as second-line therapy for patients with malignant pleural mesothelioma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8507 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8507-8507

Author(s):

Dean Anthony Fennell ◽

Angela Claire Casbard ◽

Catharine Porter ◽

Robin Rudd ◽

Jason Francis Lester ◽

...

Keyword(s):

Clinical Trial ◽

Treatment Option ◽

Malignant Pleural Mesothelioma ◽

Hazard Ratio ◽

Clinical Activity ◽

Pleural Mesothelioma ◽

Off Label Use ◽

Off Label ◽

The Impact ◽

Label Use

8507 Background: All patients with malignant pleural mesothelioma (MPM) eventually relapse following standard chemotherapy. However, there is no standard treatment option in this setting. Vinorelbine, exhibits useful clinical activity but has not been formally evaluated in a randomised clinical trial, despite its widespread off-label use worldwide. BRCA1 regulates spindle assembly checkpoint in MPM and predicts vinorelbine sensitivity in preclinical models [1,2], suggesting that BRCA1 negative patients may be chemoresistant. Methods: VIM, a Cancer Research UK funded, investigator-initiated randomised controlled phase 2 multi-centre UK trial, enrolled patients with MPM who had progressed after first-line chemotherapy. Pts were randomised 2:1 to either vinorelbine (60mg/m2 weekly Q21d escalating to 80mg/m2 from cycle 2) + active supportive care (ASC) versus ASC until disease progression, unacceptable toxicity or withdrawal of consent. The primary outcome was progression free survival (PFS) defined as the time from randomisation to any progression (based on Modified RECIST criteria for assessment of response in malignant pleural mesothelioma) or death. The trial had 90% power to detect a hazard ratio of 0.65 at the one-sided 20% significance level. Secondary endpoints were overall survival (OS), tolerability and safety. Results: Between May 2016 and Oct 2018, 154 patients were recruited from 10 UK sites and randomised to vinorelbine + ASC (n=98) or ASC alone (n=56). In the Intention-to-treat analysis, after 129 events, median PFS was 4.2 months (m) for vinorelbine + ASC compared to 2.8m for ASC alone (Hazard Ratio (HR) 0.59; 95% CI: 0.41 to 0.85; one-sided p = 0.0017). 108 deaths were reported. Median OS was 9.3m for vinorelbine + ASC compared to 9.1m for ASC alone (HR=0.79; 95% CI: 0.53 to 1.17; two-sided p = 0.24). Toxicity data and subgroup analyses including the impact of BRCA1 deficiency will be presented. Conclusion: The trial met its primary endpoint. Vinorelbine demonstrates useful clinical efficacy in relapsed MPM, supporting its off-label use, as a treatment option for patients with relapsed MPM.[1] Busacca et al, J Pathol 2012, 227(2), 200. [2] Busacca et al, Mol Cancer Res, 2021, 20(2) 379. Clinical trial information: NCT02139904.

Download Full-text

Modeling the Influence of Vaccine Administration on COVID-19 Testing Strategies

Viruses ◽

10.3390/v13122546 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2546

Author(s):

Jonathan E. Forde ◽

Stanca M. Ciupe

Keyword(s):

Mathematical Model ◽

Severe Acute Respiratory Syndrome ◽

Vaccine Administration ◽

Multi Scale ◽

Testing Strategies ◽

The Impact

Vaccination is considered the best strategy for limiting and eliminating the COVID-19 pandemic. The success of this strategy relies on the rate of vaccine deployment and acceptance across the globe. As these efforts are being conducted, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is continuously mutating, which leads to the emergence of variants with increased transmissibility, virulence, and resistance to vaccines. One important question is whether surveillance testing is still needed in order to limit SARS-CoV-2 transmission in a vaccinated population. In this study, we developed a multi-scale mathematical model of SARS-CoV-2 transmission in a vaccinated population and used it to predict the role of testing in an outbreak with variants of increased transmissibility. We found that, for low transmissibility variants, testing was most effective when vaccination levels were low to moderate and its impact was diminished when vaccination levels were high. For high transmissibility variants, widespread vaccination was necessary in order for testing to have a significant impact on preventing outbreaks, with the impact of testing having maximum effects when focused on the non-vaccinated population.

Download Full-text

Prescribing Drugs not in Accordance with the Official Instructions for Medical Use (Off-label), Clinical Guidelines, Standards of Medical Care and Legal Regulation in the Russian Federation. Part 2

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2021-04-01 ◽

2021 ◽

Vol 17 (2) ◽

pp. 286-293

Author(s):

A. R. Navasardyan ◽

S. Yu. Martsevich ◽

P. G. Gabay

Keyword(s):

Medical Care ◽

Clinical Guidelines ◽

Alternative Therapy ◽

Legal Regulation ◽

Legal Aspects ◽

Point Of View ◽

Off Label ◽

Guidelines And Standards ◽

The Impact

Prescribing drugs not in accordance with the official instructions for medical use (off-label) has medical and legal aspects. From a medical point of view, such an appointment can be dictated by clinical urgency, when there is no alternative therapy, and on the other hand, doctors often prescribe off-label drugs unknowingly, and also when there is another drug with registered indications. The article analyzes the regulations governing such appointments. The article describes possible inconsistencies between clinical guidelines and standards of medical care in this matter, the role of the medical commission, the impact on the quality and safety of medical care, as well as the types of legal liability of a medical worker that may arise when a drug is prescribed not according to instructions.

Download Full-text

Manifestations of History

10.1093/oso/9780199469864.003.0006 ◽

2017 ◽

Author(s):

Philipp Zehmisch

Keyword(s):

Economic System ◽

Black Market ◽

The State ◽

Politics Of Recognition ◽

Market Sector ◽

Freedom Fighters ◽

The Law ◽

The Impact ◽

Historical Legacies

Chapter 5 analyses manifestations of history, that is, concrete historical legacies of power and knowledge in present-day Andaman society. The first section discusses the impact of hegemonic nationalist rhetoric—highlighting the role of bourgeois nationalist freedom fighters incarcerated in the Andamans—on the local sense and perception of history. The first section aims to show how politics of recognition influence the ways in which community actors constitute their present by narrating the subaltern past. The second section focuses on the manifestation of criminality as a crucial relation between the state and the population in the here and now. It shows that Andaman actors construct contemporary identities by referring to the criminal past of convicts deported to the islands; moreover, the institutionalization of criminality within the economic system of the Andaman divides the population into elite actors profiting from the black-market sector and subalterns whose participation in the same system brings them into continuous conflict with the law.

Download Full-text

Medicines for the Treatment Of COVID-19: Awaiting the Evidence

Acta Médica Portuguesa ◽

10.20344/amp.13908 ◽

2020 ◽

Vol 33 (7-8) ◽

pp. 500

Author(s):

Natalia Marto ◽

Emília C. Monteiro

Keyword(s):

Clinical Trials ◽

Severe Acute Respiratory Syndrome ◽

The Novel ◽

Off Label Use ◽

Promising Candidate ◽

Off Label ◽

Health Authorities ◽

Investigational Drugs ◽

The World ◽

Repurposed Drugs

The novel severe acute respiratory syndrome coronavirus 2 is the cause of Coronavirus Disease 2019, a new illness with no effective treatment or vaccine that has reached pandemic proportions. In this document, we analyze how health authorities and agencies around the world position themselves regarding the off-label use of repurposed drugs or new investigational drugs to treat Coronavirus Disease 2019. We review the most promising candidate medicines, including available evidence, clinical recommendations and current options for access. Our concluding remarks stress the importance of administering off-label and investigational drugs in the setting of clinical trials, or at least in standardized scenarios, to generate as much scientific knowledge as achievable while engaging in the best efforts to treat patients and save lives.

Download Full-text

Inferior Vena Cava Filters—Current Role and Controversies

Journal of Clinical Interventional Radiology ISVIR ◽

10.1055/s-0039-1685236 ◽

2019 ◽

Vol 03 (01) ◽

pp. 037-043

Author(s):

Harit Kapoor ◽

Driss Raissi

Keyword(s):

Venous Thromboembolism ◽

Inferior Vena Cava ◽

Inferior Vena ◽

Vena Cava ◽

Off Label Use ◽

Current Role ◽

Off Label ◽

Inferior Vena Cava Filters ◽

Vena Cava Filters

AbstractInferior vena cava filters (IVCFs) remain an indispensable part of an interventionalist's toolbox. Increased recognition of filter-related complications, largely from off-label use and casual approach to filter retrieval, has led to tremendous uncertainty surrounding their use. More stringent regulations on their use and development of newer and safer anticoagulants are gradually changing their role in the management of venous thromboembolism. Herein, the authors review the current role of IVCFs, indications for their use and retrieval, as well as filter-related complications.

Download Full-text

Unapproved Uses of Approved Drugs: The Physician, the Package Insert, and the Food and Drug Administration: Subject Review

PEDIATRICS ◽

10.1542/peds.98.1.143 ◽

1996 ◽

Vol 98 (1) ◽

pp. 143-145 ◽

Cited By ~ 3

Author(s):

Keyword(s):

Drug Administration ◽

Food And Drug Administration ◽

Age Groups ◽

Package Insert ◽

Age Group ◽

Off Label Use ◽

Off Label ◽

Fda Approval ◽

Approved Drugs

Physicians who prescribe a new drug that has not been approved for a specific indication or a specific age group frequently find themselves in a quandary. Physicians who prescribe "old," time-honored drugs usually do not consult the package insert or search for US Food and Drug Administration (FDA) approval. This statement was written to clarify the legal and informational status of the package insert and the role of the FDA in approving or not approving drugs for specific indications or specific age groups. The unapproved use of approved drugs, or so-called "off-label" use, is extremely prevalent among physicians who care for children. It is important that such use of compounds be brought up to date with current FDA policies and to emphasize the responsibility of the prescribing physician in the use of these compounds.

Download Full-text

Vitamin supplementation as a potential adjunctive therapeutic approach for COVID-19: biological and clinical plausibility

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2021-0111 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Amin Daei Sorkhabi ◽

Aila Sarkesh ◽

Alireza Daei Sorkhabi ◽

Taher Entezari-Maleki ◽

Jalil Rashedi ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

21St Century ◽

Human Population ◽

Potential Role ◽

Clinical Manifestations ◽

Vitamin Supplementation ◽

Immunomodulatory Activity ◽

Off Label ◽

Pharmaceutical Interventions

Abstract The recent pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19) has introduced itself into the human population in the 21st century after the coronavirus diseases SARS-CoV and Middle East respiratory syndrome (MERS-CoV). Major investigations are underway worldwide in the search for pharmaceutical interventions for COVID-19 and many agents are administered in off-label routes. Several cases are under study to check or restrict clinical manifestations of COVID-19. According to the fact that the efficacy of some micro-nutrients like vitamins is proven to treat or prevent infectious diseases because of their antimicrobial and immunomodulatory activity, the potential role of vitamins in the COVID-19 treatment or prevention must be considered.

Download Full-text

Symptomatic severe acute respiratory syndrome coronavirus 2 reinfection in a lupus patient treated with hydroxychloroquine: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-021-03159-9 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Astrid Muyldermans ◽

Piet Maes ◽

Tony Wawina-Bokalanga ◽

Tine Anthierens ◽

Olivier Goldberg ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Humoral Immunity ◽

Lupus Erythematosus ◽

Detrimental Effect ◽

First Episode ◽

African Origin ◽

Case Presentation ◽

Black African ◽

The Impact

Abstract Background Hydroxychloroquine and chloroquine have been used for hospitalized coronavirus disease 2019 patients because of their antiviral and anti-inflammatory function. However, little research has been published on the impact of the immunomodulatory effect of (hydroxy)chloroquine on humoral immunity. Case presentation We report a case of symptomatic severe acute respiratory syndrome coronavirus 2 reinfection, diagnosed 141 days after the first episode, in a 56-year-old man of Black African origin treated with hydroxychloroquine for lupus erythematosus. No anti-severe acute respiratory syndrome coronavirus 2 IgG antibodies could be detected 127 days after the initial episode of coronavirus disease 2019. Conclusions The treatment with hydroxychloroquine probably explains the decreased immune response with negative serology and subsequent reinfection in our patient. As humoral immunity is crucial to fight a severe acute respiratory syndrome coronavirus 2 infection, the use of (hydroxy)chloroquine is likely to have a detrimental effect on the spread of the virus. This case emphasizes that more needs to be learned about the role of antibodies in protecting against severe acute respiratory syndrome coronavirus 2 (re)infection and the role of (hydroxy)chloroquine on humoral immunity.

Download Full-text