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- Page navigation anchor for RE: Revisiting G6PD deficiency amidst COVID-19 pandemicRE: Revisiting G6PD deficiency amidst COVID-19 pandemic
Hydroxychloroquine (HCQ) use has been promoted recently in tackling the infection with severe acute respiratory syndrome coronavirus 2 in the current pandemic of coronavirus disease 2019 (COVID-19).1 Until the results of the clinical trials are available, the current body of literature supports the prophylactic use of HCQ among the high risk groups.2 However a clear informed choice needs to be offered to every contact for the potential risks and benefits that this drug has to offer. What needs a pointer is the possible risk of development of hemolytic anemia when prescribing HCQ to individuals with Glucose 6 Phosphate Dehydrogenase (G6PD) deficiency.3
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G6PD deficiency is the commonest red blood cell enzymatic deficiency and the most common hereditary disorder in the world, affecting nearly 330 million people worldwide accounting for a global prevalence of 4.9%.3 Over 200 G6PD gene mutations have been reported. This enzyme protects against the oxidative stress. Infection, stress may precipitate hemolysis in individuals with the enzyme deficiency. The awareness of epidemiological distribution of the genotypic variants of G6PD deficiency that determines the severity of hemolysis is of prime importance. The Mediterranean type being severe is more prevalent in Europe, Asia, and northern India, and the African variant is commonly observed among individuals of African descent and the African Americans.3 The authors quoted a largest study from the United States in rheumatolog...Competing Interests: None declared.References
- David N. Juurlink. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ 2020;192:E450-E453.
- Chatterjee P, Anand T, Singh JK, Rasaily R, Singh R, Das S, et al. Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19. 2001 [cited 2020 Jun 4]; Available from: http://www.ijmr.org.in/preprintarticle
- Beauverd Y, Adam Y, Assouline B, Samii K. COVID-19 infection and treatment with hydroxychloroquine cause severe haemolysis crisis in a patient with glucose-6-phosphate dehydrogenase deficiency. Eur J Haematol. 2020 Apr 23;10.1111/ejh.13432.
- Marmor MF. COVID-19 and Chloroquine/Hydroxychloroquine: Is There Ophthalmological Concern? Am J Ophthalmol. 2020 May 8; S0002-9394(20)30140-9. doi: 10.1016/j.ajo.2020.03.029.
- Jiang S, Choudhry N. OCT Angiographic Findings in Glucose-6-Phosphate Dehydrogenase Deficiency. Ophthalmic Surg Lasers Imaging Retina. 2017 01;48(8):664–7.
- Page navigation anchor for Is Hydrochloroquine safe with a personality disorder ?Is Hydrochloroquine safe with a personality disorder ?
Collecting good quality clinical data on the use of HCLO in COVID-19 is still ongoing with many controversial discussions of the evidence. Individuals and pressure groups have called for widespread prescription of these drugs. Precautions have to be taken because of the psychiatric vulnerability in some individual and the psychiatric side effects of this drug (1,2). A recent meta-analytical review (3) indicated that the population with Ultra High Risk Psychosis includes a large subgroup with severe personality pathology, which may present with attenuated psychotic symptoms along with distinct and very heterogeneous personality traits.
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The DSM-5 lists several types of personality disorder into clusters based on similar characteristics. The narcissistic personality (NPD) is characterized by fantasies or grandiose behaviors, a need for admiration and a lack of empathy.The borderline personality (BPD) is characterized by marked impulsivity and instability in interpersonal relationships, self-image and affects. The histrionic personality is characterized by excessive emotional responses and a quest for attention. The Antisocial: social irresponsibility, contempt for others, and manipulation for personal gain. Patients with NPD might show an intact cognitive empathy capacity and can identify with the thoughts, and intentions of others but capacity for emotional empathy is compromised. The signs of NPD are often more visible in organizational, social, family and legal conte...Competing Interests: None declared.References
- . Is Hydrochloroquine safe with a personality disorder ?. 2020;:-.
- 2.Stip, E. RE: Hydrochloroquine, Covid-19 and psychiatry. CMAJ. 2020.
- 3. Boldrini T, Tanzilli A, Pontillo M, et al. Comorbid Personality Disorders in Individuals With an At-Risk Mental State for Psychosis: A Meta-Analytic Review [published correction appears in Front Psychiatry. 2020 May 12;11:235]. Front Psychiatry. 2019;1
- 4.Gonzalez-Nieto, J. A., and E. Costa-Juan. "Psychiatric symptoms induced by hydroxychloroquine." Lupus 24.3 (2015): 339.
- 5.Ferrando, Stephen J., et al. "COVID-19 Psychosis: A potential new neuropsychiatric condition triggered by novel coronavirus infection and the inflammatory response?." Psychosomatics (2020).
- Page navigation anchor for RE: Oral Contraceptive Pills May be Better and Safe in the Management of COVID-19 than Chloroquine derivatives!RE: Oral Contraceptive Pills May be Better and Safe in the Management of COVID-19 than Chloroquine derivatives!
The management of COVID-19 is largely supportive, and the cause of death is respiratory failure from acute respiratory distress syndrome (ARDS). Chloroquine derivatives were tried with little clinical evidence despite abundant evidence on their 'side-effects' (1). We should re-purpose safer drugs. COVID-19 which has infected about 3000000 people and killed about 200000. COVID-19 has killed more men than women. For example, from the data from New York City Health as of April 14, 61,8% of the people who died are men (2). It is possible that sex hormones are offering some degree of protection from COVID19. There are some reports that the virus may reside in testicles which act as a reservoir although less likely. Accumulating evidence suggests that a significant proportion of the morbidity and mortality in patients with severe COVID-19 might be due to a cytokine storm syndrome and patients die because of the abnormal immune response that direct insult from the virus. It is known that estrogens and progesterone have immunomodulatory functions (3, 4). Estrogen plays a role in the modulation of lymphocyte survival and expansion and in the expression of Th1 versus Th2 cytokines (3). ᵞ/ᵟ TCR+ cells express progesterone receptors upon antigen exposure. Subsequent progesterone binding results in the synthesis of a protein named the progesterone-induced blocking factor (PIBF). PIBF through its action on phospholipase A2 enzyme interferes with arachidonic acid metabolism a...
Show MoreCompeting Interests: None declared.References
- . RE: Oral Contraceptive Pills May be Better and Safe in the Management of COVID-19 than Chloroquine derivatives!. 2020;:-.
- Bhopal, Raj. "Covid-19 worldwide: we need precise data by age group and sex urgently." bmj 369 (2020).
- Lang, Thomas J. "Estrogen as an immunomodulator." Clinical immunology 113.3 (2004): 224-230.
- Szekeres-Bartho, Julia, et al. "Progesterone as an immunomodulatory molecule." International immunopharmacology 1.6 (2001): 1037-1048.
- Sutton, Desmond, et al. "Universal screening for SARS-CoV-2 in women admitted for delivery." New England Journal of Medicine (2020).
- Page navigation anchor for RE: Is it ethical to use chloroquine for treatment of SARS-CoV-2?RE: Is it ethical to use chloroquine for treatment of SARS-CoV-2?
Since the novel coronavirus (SARS-CoV-2) outbreak in China last December 31, 2019, several protocols were published on its diagnosis and treatment. Chloroquine, a known antimalarial drug, was among the treatments suggested to be effective in treating SARS-CoV-2 [1].
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Last April 27, 2020, Juurlink summarized well the potential hazards associated with the use of chloroquine and hydroxychloroquine [2]
A comprehensive search in PubMed from July 1966 till January 1, 2020 identified 20 publications about coronaviruses and chloroquine. Of which, 16 publications were in-vitro and in-vitro experiments and 4 were reviews. Identified studies were published between 1987 and 2019. None of the recent recommendations to treat SARS-CoV-2 with chloroquine were based on randomized controlled clinical trials (RCTs). Also, the recommendations included various doses and regimens, some of which combined chloroquine with other drugs like Azithromycin [1,3].
A recent report of the European Medicine Agency recommended chloroquine for treatment of SARS-CoV-2 only in RCTs or emergency use programmes [4]. In Sweden, several hospitals stopped using chloroquine for treating SARS-CoV-2 after reports of several severe side effects [5]. Undoubtedly, Phase II and III RCTs are needed to assess the efficacy and adverse events of chloroquine in treating SARS-CoV-2.
This raises the questions: is the current use of chloroquine, while awaiting RCTs results, ethical? Should we not wait for...Competing Interests: None declared.References
- , . RE: Is it ethical to use chloroquine for treatment of SARS-CoV-2?. 2020;:-.
- Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ 2020;192:E450-E453.
- Centre for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19) Information for Clinicians on Therapeutic Options for Patients with COVID-19 Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html
- European Medicines Agency. COVID-19: chloroquine and hydroxychloroquine only to be used in clinical trials or emergency use programmes. Available at: https://www.ema.europa.eu/en/
- Mccall R. Some Swedish hospitals have stopped using chloroquine to treat covid-19 after reports of severe side effects. Newsweek [on April 6, 2020]. Available at: https://www.newsweek.com/swedish-hospitals-chloroquine-covid-19-side-effects-1496368
- Page navigation anchor for RE:Drug doses and safety of chloroquine/hydroxychloroquineRE:Drug doses and safety of chloroquine/hydroxychloroquine
In his timely review,(1) Dr Juurlink points out hazards associated with the use of chloroquine (CQ) and hydroxychloroquine (HCQ). As more information about the use of these drugs in COVID-19 patients is becoming available, some investigators administer CQ or HCQ according to their base content, while others administer them according to their salt content. This can become quite problematical when comparing the toxicity and efficacy of different drug regimens.
For example, in a recent study,(2) a total dose of 12 g of CQ base, given over 10 days, was associated with severe adverse events and quite a number of deaths. This high dose was apparently based on a previous study,(3) conducted elsewhere, in which it was presumed that 10g over 10 days had been well tolerated. In actual fact, patients in the previous study had received only 6 g of CQ base because their CQ dose had been based on the CQ diphosphate salt content (CQ tablets contain 250mg CQ salt and 150mg CQ base). A much lower dose is of course used for malaria treatment (1.5g over 3 days) and doses are invariably expressed in terms of base content. This is because various salts, with different CQ base contents, were introduced in the 1950's and 1960s for the treatment of malaria.
Although HCQ is an antimalarial, it is not used frequently these days to treat malaria. It is of course used extensively for treating autoimmune diseases, and doses are usually administered according to their salt content (H...
Show MoreCompeting Interests: None declared.References
- 1. Juurlink DN. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ 2020, 192 (17) E450-E453.
- 2. Borba MGS, Val FFA, Sampaio VS, et al. Effect of High vs Low Doses of Chloroquine Diphosphate as Adjunctive Therapy for Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Clinical Trial. JAMA
- 3. Expert concensus on chloroquine phosphate for the treatment of novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 2020; 43(3):185-188.
- Page navigation anchor for RE: Hydrochloroquine, Covid-19 and psychiatryRE: Hydrochloroquine, Covid-19 and psychiatry
Juurlink(1) summarizes well and briefly the neuropsychiatric side effects (NSE) of chloroquine (CLO) and hydrochloroquine (HCLO). In addition to banal and not exceptional NSE such as insomnia, anxiety, nervousness, psychomotor excitement, HCLO can cause serious NSE(2,3). They have been described during the treatment of malaria, but also in dermatology and rheumatology. In my career I have only seen three cases of psychosis. The clinical presentation is fairly consistent from one observation to another: occurring in a patient with no psychiatric history of manifestations of delusion, hallucinations, manic episode, or depression, after a period of a few hours to 40 days, yielding on average one week after stopping CLO. There is no correlation with the dose administered. In a MedLine search, I identified 113 NSE case reports in the literature and 2 meta-analysis. Currently, HCLO is gaining more attention as a potential antiviral agent for the coronavirus. However, I am surprised that there are no more consideration in the current protocols for documenting NSE. More than 6500 patients will potentially be included in research protocols with HCLO. In the clinical registries, only one trial mentions an exclusion criterion (citalopram, suicidal thoughts) and another one takes into account psychiatric effects. That's all. Psychiatric variables don't matter. In articles on HCLO and COVID(4), few data on psychiatric signs are mentioned: is it an absence of events or an abse...
Show MoreCompeting Interests: None declared.References
- . RE: Hydrochloroquine, Covid-19 and psychiatry. 2020;:-.
- Bitta MA, Kariuki SM, Mwita C, Gwer S, Mwai L, Newton CRJC. Antimalarial drugs and the prevalence of mental and neurological manifestations: A systematic review and meta-analysis. Wellcome Open Res. 2017;2:13. Published 2017 Jun 2. doi:10.12688/wellcomeop
- Bryan Grabias & Sanjai Kumar (2016) Adverse neuropsychiatric effects of antimalarial drugs, Expert Opinion on Drug Safety, 15:7, 903-910, DOI: 10.1080/14740338.2016.1175428
- Raoult, D., Hsueh, P. R., Stefania, S., & Rolain, J. M. (2020). VSI: COVID-19 Therapeutic. International journal of antimicrobial agents, 105937
- Chevance, A., Gourion, D., Hoertel, N., Llorca, P. M., Thomas, P., Bocher, R., ... & Masson, M. (2020). Assurer les soins aux patients souffrant de troubles psychiques en France pendant l’épidémie à SARS-CoV-2. L'Encéphale
- Page navigation anchor for The "unbridled race" for using chloroquine and hydroxychloroquine to prevent or treat COVID-19 leads to shortages for patients with chronic inflammatory conditions and malaria in BrazilThe "unbridled race" for using chloroquine and hydroxychloroquine to prevent or treat COVID-19 leads to shortages for patients with chronic inflammatory conditions and malaria in Brazil
In April 8, 2020, Dr. David Juurlink provided an overview of potential harms associated with use of chloroquine (CQ) and hydroxychloroquine (HCQS) and suggested that the surge in prescriptions of these drugs based on speculation to COVID-19 prevention or treatment threatens the availability of these drugs for patients with malaria and chronic inflammatory disorders for whom they are known to be effective (1). Indeed, the urgent need for treatment imposed by the COVID-19 pandemic has led to the broadcast of misinformation on efficacy and safety of medications, which may have led people to an “unbridled race” for CQ and HCQS.
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This scenario is not promising in low- and middle-income countries. Brazil has one of the highest prevalence estimates of systemic lupus erythematous and rheumatoid arthritis worldwide and contributes to 40% of malaria cases in the Americas. Malaria transmission remains endemic in the Amazon Basin, which accounts for 99.5% of the country’s malaria burden (2). Worryingly, COVID-19 cases in Brazil and Amazon region has increased considerably. Recently, The Brazilian National Health Surveillance Agency (ANVISA) published a rule that classifies CQ and HCQS as special control drugs to restrict access to these medications in pharmacies and avoiding shortages. However, we have found a dramatically driven up demand for these drugs and the stocks at various pharmacies are depleted. A similar phenomenon has also been reported in African countries, where peo...Competing Interests: None declared.References
- 1. David N. Juurlink. Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. CMAJ 2020;10.1503/cmaj.200528.
- 2. Marcelo U. Ferreira, Marcia C. Castro. Challenges for malaria elimination in Brazil. Malar J. 2016; 10.1186/s12936-016-1335-1.
- 3. Jack Goodman, Christopher Giles. Coronavirus and chloroquine: Is there evidence it works? BBC News. 2020. Available from: https://www.bbc.com/news/51980731
- 4. Charles Piller. ‘This is insane!’ Many scientists lament Trump’s embrace of risky malaria drugs for coronavirus. Science. 2020; 10.1126/science.abb9021.
- 5. Shao Liu, Ping Luo, Mimi Tang, Qin Hu, Joseph P. Polidoro, Shusen Sun, Zhicheng Gong. Providing pharmacy services during the coronavirus pandemic. Int J Clin Pharm. 2020; 10.1007/s11096-020-01017-0.
- Page navigation anchor for RE: Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infectionRE: Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection
Juurlink's timely and otherwise thorough review of chloroquine, hydroxychloroquine and azithromycin(1) omitted an important safety consideration for azithromycin that is relevant to recipients of allogeneic blood and marrow transplantation (BMT). In these patients, azithromycin may be prescribed to prevent or treat transplant-related lung disease (especially bronchiolitis obliterans). However, in a recent randomized controlled trial in BMT recipients, patients assigned to receive prophylactic azithromycin experienced significantly higher relapse rates of their underlying hematological malignancies, as well as an increase in overall mortality(2). This serious safety concern led Health Canada in 2018 to distribute a warning to prescribers and patients about the use of azithromycin in BMT recipients(3). As BMT recipients are often profoundly immune suppressed, SARS-CoV-2 infection may be more common and severe. Prescribers should thus be cognizant of this potentially serious adverse effect of azithromycin in BMT recipients.
Competing Interests: None declared.References
- . RE: Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection. 2020;:-.
- 2. Bergeron A, Chevret S, Granata A, Chevallier P, Vincent L, Huynh A, et al. Effect of Azithromycin on Airflow Decline-Free Survival After Allogeneic Hematopoietic Stem Cell Transplant: The ALLOZITHRO Randomized Clinical Tr
- 3. https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2018/67430a-eng.php. Accessed April 8 2020.