Use Of Antimalarials Research Articles

Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population-Based Study in Emilia-Romagna, Northern Italy.

ObjectiveTo evaluate the susceptibility to coronavirus disease 2019 (COVID‐19) in patients with autoimmune conditions treated with antimalarials in a population‐based study.MethodsAll residents treated with chloroquine (CQ)/hydroxychloroquine (HCQ) from July through December 2019 and living in 3 provinces of Regione Emilia‐Romagna were identified by drug prescription registries and matched with the registry containing all residents living in the same areas who have had swabs and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.ResultsA total of 4,408 patients were identified. The prevalence of patients receiving antimalarials was 0.85 per 1,000 men and 3.3 per 1,000 women. The cumulative incidence of testing during the study period was 2.7% in the general population and 3.8% among those receiving CQ or HCQ, while the cumulative incidence of testing positive was 0.55% in the general population and 0.70% among those receiving CQ/HCQ. Multivariate models showed that those receiving CQ/HCQ had a slightly higher probability of being tested compared to the general population (OR 1.09 [95% CI 0.94–1.28]), the same probability of being diagnosed as having COVID‐19 (OR 0.94 [95% CI 0.66–1.34]), and a slightly lower probability of being positive once tested (OR 0.83 [95% CI 0.56–1.23]). None of the differences were significant.ConclusionOur findings do not support the use of antimalarials as a prophylactic treatment of COVID‐19.

Mathematical modelling for malaria under resistance and population movement

In this work, two mathematical models for malaria under resistance are presented. More precisely, the first model shows the interaction between humans and mosquitoes inside a patch under infection of malaria when the human population is resistant to antimalarial drug and mosquitoes population is resistant to insecticides. For the second model, human–mosquitoes population movements in two patches is analyzed under the same malaria transmission dynamic established in a patch. For a single patch, existence and stability conditions for the equilibrium solutions in terms of the local basic reproductive number are developed. These results reveal the existence of a forward bifurcation and the global stability of disease–free equilibrium. In the case of two patches, a theoretical and numerical framework on sensitivity analysis of parameters is presented. After that, the use of antimalarial drugs and insecticides are incorporated as control strategies and an optimal control problem is formulated. Numerical experiments are carried out in both models to show the feasibility of our theoretical results.

Cost-effectiveness and public health impact of RTS,S/AS01E malaria vaccine in Malawi, using a Markov static model

Background: The RTS,S/AS01E malaria vaccine is being assessed in Malawi, Ghana and Kenya as part of a large-scale pilot implementation programme. Even if impactful, its incorporation into immunisation programmes will depend on demonstrating cost-effectiveness. We analysed the cost-effectiveness and public health impact of the RTS,S/AS01E malaria vaccine use in Malawi. Methods: We calculated the Incremental Cost Effectiveness Ratio (ICER) per disability-adjusted life year (DALY) averted by vaccination and compared it to Malawi’s mean per capita Gross Domestic Product. We used a previously validated Markov model, which simulated malaria progression in a 2017 Malawian birth cohort for 15 years. We used a 46% vaccine efficacy, 75% vaccine coverage, USD5 estimated cost per vaccine dose, published local treatment costs for clinical malaria and Malawi specific malaria indicators for interventions such as bed net and antimalarial use. We took a healthcare provider, household and societal perspective. Costs were discounted at 3% per year, no discounting was applied to DALYs. For public health impact, we calculated the DALYs, and malaria events averted. Results: The ICER/DALY averted was USD115 and USD109 for the health system perspective and societal perspective respectively, lower than GDP per capita of USD398.6 for Malawi. Sensitivity analyses exploring the impact of variation in vaccine costs, vaccine coverage rate and coverage of four doses showed vaccine implementation would be cost-effective across a wide range of different outcomes. RTS,S/AS01 was predicted to avert a median of 93,940 (range 20,490–126,540) clinical cases and 394 (127–708) deaths for the three-dose schedule, or 116,480 (31,450–160,410) clinical cases and 484 (189–859) deaths for the four-dose schedule, per 100 000 fully vaccinated children. Conclusions: We predict the introduction of the RTS,S/AS01 vaccine in the Malawian expanded programme of immunisation (EPI) likely to be highly cost effective.

Diagnosis and treatment analysis of malaria in Changsha, 2017-2018

Objective To understand the basic situation of diagnosis and treatment of malaria cases, so as to provide scientific basis for the prevention and control of malaria. Methods Investigations were conducted on telephone surveys and clinical data review for malaria cases reported in Changsha in 2017-2018. Results A total of 70 malaria cases were investigated, and the diagnostic accuracy of the first time to the hospital was significantly higher in the medical institutions above the county level (88%) than below (5%). Time interval between initial visit and diagnosis was in line with the national level. Univariate analysis revealed that the factors impacting the time interval were‘Consulting the CDC staffs’, ‘Whether the doctor asked the epidemiological history’and‘the patients’ knowledge of malaria’ ( P <0.05). Logistic regression analysis indicated that the time interval was correlated to‘Whether the doctor asked the epidemiological history’, and the difference has statistical significance ( P <0.05). The rate of appropriate use of antimalarial drugs was 74.29%, statistic difference ( P <0.05) was found at different years, types of malaria and methods of medication (oral or injection). Conclusion We should enhance the self-protection awareness of key groups, strengthen the awareness and ability of malaria diagnosis and treatment in medical institutions, especially primary medical institutions. 摘要：目的 了解疟疾病例诊治基本情况, 为提出针对性疟疾防控措施提供科学依据。 方法 对 2017—2018 年 长沙市报告的疟疾病例进行普查, 采取电话回访病例及查阅病例资料的方式开展。 结果 共调查 70 例疟疾病例, 病 例在县级以上医疗机构初诊正确率(88%)显著高于县级以下医疗机构(5%); 病例就诊-确诊时间间隔基本与全国水平持 平, 对就诊-确诊时间间隔影响因素进行单因素分析, 结果显示“就诊前咨询疾控机构”、“就诊时医生询问流行病学史” 及“病例有疟疾认知”差异有统计学意义( P <0.05), 进一步开展 Logistic 回归分析显示, “就诊时医生询问流行病学史”差 异有统计学意义( P <0.05); 病例抗疟药使用规范率为 74.29%, 不同年度、不同疟疾类型及不同用药方式(口服或注射)抗 疟药使用规范率差异有统计学意义( P <0.05)。 结论 今后应提高重点人群自我防护意识, 提高医疗机构尤其是基层医 疗机构疟疾诊治意识及能力。

Recombinant C-Terminal Domains from Scorpine-like Peptides Inhibit the Plasmodium berghei Ookinete Development In Vitro

Malaria is a parasitic disease, caused by protozoa of the genus Plasmodium, and is transmitted to humans through the bites of infected Anopheles mosquitoes. More than 200 million cases of malaria are reported annually and about 400,000 deaths worldwide. Currently, the use of antimalarial drugs has been efficient in most cases, however, resistance to these drugs is increasing, making it necessary and essential to have a new range of possible drugs or medicines to combat this disease. Scorpion venom contains peptides whose functions are now intensively studied. Some of these peptides are known as Scorpine-like, which have anti-bacterial and antiplasmodial properties as they have been described to inhibit the development of parasites responsible for malaria. Scorpine-like peptides are composed of two structural domains: one α-helical N-terminal domain, and a C-terminal domain with the cysteine-stabilized α/β motif, which confers the peptide the function of blocking potassium channels and/or anti-bacteria activity. In this work, two C-terminal domains from Scorpine-like peptides were constructed and expressed in Escherichia coli, and their function was analyzed. We were able to demonstrate that the recombinant C-terminal domains rCterVm and rCterHg showed antiplasmodial activity producing 60% and 90% inhibition, respectively, of Plasmodium berghei development at 1 µM and 0.15 µM concentration, which makes these peptides promising candidates against Malaria.

Teratogen update: Malaria in pregnancy and the use of antimalarial drugs in the first trimester.

Malaria is a particular problem in pregnancy because of enhanced sensitivity, the possibility of placental malaria, and adverse effects on pregnancy outcome. Artemisinin-containing combination therapies (ACTs) are the most effective antimalarials known. WHO recommends 7-day quinine therapy for uncomplicated Plasmodium falciparum malaria in the first trimester despite the superior tolerability and efficacy of 3-day ACT regimens because artemisinins caused embryolethality and/or cardiovascular malformations at relatively low doses in rats, rabbits, and monkeys. The developmental toxicity of artesunate, artemether, and DHA were similar in rats but artesunate was embryotoxic at lower doses in rabbits (5 mg/kg/day) than artemether (no effect level = 25 mg/kg/day). In clinical studies in Africa, treatment with artemether-lumefantrine in the first trimester was observed to be highly efficacious and the miscarriage rate (≤3.1%) was similar to no antimalarial treatment (2.6%). When data from the first-trimester use of largely artesunate-based therapies in Thailand were pooled together, there was no difference in miscarriage rate compared to quinine. However, individually, artesunate-mefloquine was associated with a higher miscarriage rate (15/71 = 21%) compared to other artemisinin-based therapies including 7-day artesunate + clindamycin (2/50 = 4%) and quinine (92/842 = 11%). Thus, appropriate statistical comparisons of individual ACT groups are needed prior to assuming that they all have the same risk for developmental toxicity. Current limitations in the assessment of the safety of ACTs in the first trimester are a lack of exposures early in gestation (gestational weeks 6-7), limited postnatal evaluation for cardiovascular malformations, and the pooling of all ACTs for the assessment of risk.

Impact of Chronic Use of Antimalarials on SARS-CoV-2 Infection in Patients With Immune-Mediated Rheumatic Diseases: Protocol for a Multicentric Observational Cohort Study.

BackgroundCOVID-19, caused by the virus SARS-CoV-2, has brought extensive challenges to the scientific community in recent months. Several studies have been undertaken in an attempt to minimize the impact of the disease worldwide. Although new knowledge has been quickly disseminated, including viral mechanisms, pathophysiology, and clinical findings, there is a lack of information on the effective pharmacological management of this disease. In vitro studies have shown some benefits related to the use of antimalarials (chloroquine and hydroxychloroquine) for inhibiting SARS-CoV-2. However, the data from open clinical trials on COVID-19 patients are controversial.ObjectiveWe present the protocol for a research project that compares the potential protective effect of antimalarials in preventing moderate-to-severe forms of COVID-19 in two groups: (1) patients treated chronically with antimalarials for rheumatic diseases and (2) other members of the patients’ household who have not been diagnosed with rheumatic diseases and are not taking antimalarials.MethodsThis is a 24-week, prospective, observational cohort study comprising patients from public and private health services across Brazil, who chronically use antimalarials for the treatment of immune-mediated rheumatic diseases, osteoarthritis, or chikungunya-related arthropathy. A total of six sequential phone interviews were scheduled during the COVID-19 outbreak in five different regions of Brazil. Information regarding social, epidemiological, and demographic data, as well as details about rheumatic diseases, antimalarials, comorbidities, and concomitant medication, is being recorded using a specific online form in the REDCap database. Symptoms suggestive of COVID-19, including fever, cough, dyspnea, anosmia, and dysgeusia, are being self-reported and collected via phone interviews. Our main outcomes are hospitalization, need of intensive care unit, and death.ResultsRecruitment began at the end of March 2020, and the inclusion was done during an 8-week period (from March 29 to May 17) with a total of 10,443 individuals enrolled at baseline, 5166 of whom have rheumatic diseases, from 23 tertiary rheumatology centers across 97 Brazilian cities. Data analysis is scheduled to begin after all inclusion data have been collected.ConclusionsThis study, which includes a large sample of chronic antimalarial users, will allow us to explore whether SARS-CoV-2 infection may be associated with immune-mediated rheumatic diseases and long-term antimalarial usage.Trial RegistrationBrazilian Registry of Clinical Trials RBR–9KTWX6; http://www.ensaiosclinicos.gov.br/rg/RBR-9ktwx6/International Registered Report Identifier (IRRID)DERR1-10.2196/23532

What could explain the late emergence of COVID-19 in Africa?

At the end of November 2019, a novel coronavirus responsible for respiratory tract infections emerged in China. Despite drastic containment measures, this virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread in Asia and Europe. The pandemic is ongoing with a particular hotspot in southern Europe and America in spring 2020. Many studies predicted an epidemic in Africa similar to that currently seen in Europe and the USA. However, reported data do not confirm these predictions. Several hypotheses that could explain the later emergence and spread of the coronavirus disease 2019 (COVID-19) pandemic in African countries are being discussed, including the lack of health-care infrastructure capable of clinically detecting and confirming COVID-19 cases, the implementation of social distancing and hygiene, international air traffic flows, the climate, the relatively young and rural population, the genetic polymorphism of the angiotensin-converting enzyme 2 receptor, cross-immunity and the use of antimalarial drugs.

Update on antimalarials and systemic lupus erythematosus

The purpose of this review is highlighting the most recent evidence on the clinical efficacy and toxicity of antimalarials in systemic lupus erythematosus (SLE). New data confirm the effects of antimalarials in preventing SLE activity, damage and infections and in decreasing mortality. An important reduction in use of health resources is related to continued antimalarial use. Hydroxychloroquine (HCQ) may prevent preeclampsia in pregnant women with SLE. HCQ ocular toxicity is infrequent and could be associated with blood levels. Gastrointestinal and skin toxicity are underrecognized and could influence adherence. Prolongation of QT interval is extremely unusual with HCQ. Doses of HCQ of 200 mg/day seem to offer a good efficacy/toxicity balance. HCQ protection against herpes zoster and Pneumocystis jirovecii infection has been shown. On the contrary, HCQ prescription by doctors and adherence by patients are both under recommended standards. The recent coronavirus disease 2019 pandemic has resulted in a significant shortage of HCQ in many countries with possible consequences in the correct treatment of lupus patients. Recent evidence reinforces the central role of HCQ in SLE therapy. The reduction in activity, damage accrual and mortality is consistent across studies, countries and ethnical groups. On the contrary, and despite the well established beneficial effects of prolonged regular HCQ therapy, many SLE patients do never take this drug or it is eventually stopped in the setting of severe flares, pregnancy or presumed toxicity. Every effort must be made to assure the correct prescription of HCQ and not to withdraw the drug unless unequivocal signs of toxicity are present.

Antimalarial drugs inhibit the replication of SARS-CoV-2: An in vitro evaluation

In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2) causing coronavirus diseases 2019 (COVID-19) emerged in Wuhan, China. African countries see slower dynamic of COVID-19 cases and deaths. One of the assumptions that may explain this later emergence in Africa, and more particularly in malaria endemic areas, would be the use of antimalarial drugs. We investigated the in vitro antiviral activity against SARS-CoV-2 of several antimalarial drugs. Chloroquine (EC50 = 2.1 μM and EC90 = 3.8 μM), hydroxychloroquine (EC50 = 1.5 μM and EC90 = 3.0 μM), ferroquine (EC50 = 1.5 μM and EC90 = 2.4 μM), desethylamodiaquine (EC50 = 0.52 μM and EC90 = 1.9 μM), mefloquine (EC50 = 1.8 μM and EC90 = 8.1 μM), pyronaridine (EC50 = 0.72 μM and EC90 = 0.75 μM) and quinine (EC50 = 10.7 μM and EC90 = 38.8 μM) showed in vitro antiviral effective activity with IC50 and IC90 compatible with drug oral uptake at doses commonly administered in malaria treatment. The ratio Clung/EC90 ranged from 5 to 59. Lumefantrine, piperaquine and dihydroartemisinin had IC50 and IC90 too high to be compatible with expected plasma concentrations (ratio Cmax/EC90 < 0.05). Based on our results, we would expect that countries which commonly use artesunate-amodiaquine or artesunate-mefloquine report fewer cases and deaths than those using artemether-lumefantrine or dihydroartemisinin-piperaquine. It could be necessary now to compare the antimalarial use and the dynamics of COVID-19 country by country to confirm this hypothesis.

Ocular Findings in COVID-19 Patients: A Review of Direct Manifestations and Indirect Effects on the Eye.

The novel pandemic coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has challenged the medical community. While diagnostic and therapeutic efforts have been focused on respiratory complications of the disease, several ocular implications have also emerged. SARS-CoV-2 RNA has been found in tears of the infected patients, and reports suggest that the ocular surface could serve as a portal of entry and a reservoir for viral transmission. Clinically, COVID-19 has been associated with mild conjunctivitis, which can be the first and only symptom of the disease. Subtle retinal changes like hyperreflective lesions in the inner layers on optical coherence tomography (OCT), cotton-wool spots, and microhemorrhages have also been reported. In addition, COVID-19 has been associated with an increased incidence of systemic diseases like diabetes mellitus and Kawasaki disease, which are particularly relevant for ophthalmologists due to their potentially severe ocular manifestations. Several treatment strategies are currently under investigation for COVID-19, but none of them have been proved to be safe and effective to date. Intensive care unit patients, due to risk factors like invasive mechanical ventilation, prone position, and multiresistant bacterial exposure, may develop ocular complications like ocular surface disorders, secondary infections, and less frequently acute ischemic optic neuropathy and intraocular pressure elevation. Among the array of drugs that have shown positive results, the use of hydroxychloroquine and chloroquine has raised a concern due to their well-known retinal toxic effects. However, the risk of retinal toxicity with short-term high-dose use of antimalarials is still unknown. Ocular side effects have also been reported with other investigational drugs like lopinavir-ritonavir, interferons, and interleukin-1 and interleukin-6 inhibitors. The aim of this review was to summarize ophthalmological implications of SARS-CoV-2 infection to serve as a reference for eye care and other physicians for prompt diagnosis and management.

Rural\u2013urban disparities and factors associated with delayed care-seeking and testing for malaria before medication use by mothers of under-five children, Igabi LGA, Kaduna Nigeria

BackgroundFever in under-five children (U5) is the commonest presenting complaint in general practice and mothers’ recognition is an entry point for fever treatment, including malaria. This study describes rural–urban disparity in fever prevalence in U5, mothers’ malaria knowledge, care-seeking, testing for malaria before anti-malarial medication and the associated factors.MethodsA cross-sectional survey was conducted among 630 mother–child pairs [rural (300) and urban (330)] selected randomly using a multi-stage sampling from 63 villages in Igabi LGA, Kaduna State, Nigeria. Trained female data collectors administered a pre-tested structured questionnaire to collect information on mother–child demographic profiles, malaria knowledge, fever episodes in birth order last child in two weeks prior to survey, blood testing before anti-malarial use, and delayed care-seeking defined as care sought for fever > 48 h of onset. Malaria knowledge was categorized into good, average, and poor if the final scores were ≥ 75th, 50th–74th, and < 50th percentiles, respectively. Frequency, proportions, and odds ratio were calculated. Statistically significant was set at p-value < 0.05.ResultsThe median age (interquartile range) of rural mothers was 30 (IQR, 10) years compared to 27 (IQR, 6) years in urban. Of the 70.0% (441/629) U5 children with fever, 58.5% (258/441) were in rural settlements. A third of the mothers whose child had fever sought care. Mothers in rural settlements were 2.8 (adjusted OR: 2.8, CI 1.8–4.2, p < 0.01) times more likely to delay care-seeking for fever. Other significant factors were poor or no knowledge of malaria transmission, poor perception of malaria as a major health problem, and household size > 5. Also, mothers who had no formal education were four times more likely to receive anti-malarial medications without testing for malaria compared to their educated counterpart (adjusted OR: 4.0, 95% CI 1.6–9.9, p < 0.000).ConclusionsRural–urban disparities existed between fever prevalence in U5 children, care-seeking practices by their mothers, and factors associated with delayed care-seeking and testing the fever for malaria before anti-malarial medication. Fever treatment for high impact malaria elimination in Nigeria needs a context-specific intervention rather than ‘one-size-fits-all’ approach.

Antimalarial artemisinin-based combination therapies (ACT) and COVID-19 in Africa: In vitro inhibition of SARS-CoV-2 replication by mefloquine-artesunate

ObjectivesAt the end of November 2019, a novel coronavirus responsible for respiratory tract infections (COVID-19) emerged in China. Despite drastic containment measures, this virus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spread in Asia and Europe. The pandemic is ongoing with a particular hotspot in Southern Europe and America; many studies predicted a similar epidemic in Africa, as is currently seen in Europe and the United States of America. However, reported data have not confirmed these predictions. One of the hypotheses that could explain the later emergence and spread of COVID-19 pandemic in African countries is the use of antimalarial drugs to treat malaria, and specifically, artemisinin-based combination therapy (ACT).MethodsThe antiviral activity of fixed concentrations of ACT at concentrations consistent with those observed in human plasma when ACT is administered at oral doses for uncomplicated malaria treatment was evaluatedin vitro against a clinically isolated SARS-CoV-2 strain (IHUMI-3) in Vero E6 cells.ResultsMefloquine-artesunate exerted the highest antiviral activity with % inhibition of 72.1 ± 18.3 % at expected maximum blood concentration (Cmax) for each ACT drug at doses commonly administered in malaria treatment. All the other combinations, artesunate-amodiaquine, artemether-lumefantrine, artesunate-pyronaridine, or dihydroartemisinin-piperaquine, showed antiviral inhibition in the same ranges (27.1 to 34.1 %).ConclusionsAntimalarial drugs for which concentration data in the lungs are available are concentrated from 10 to 160 fold more in the lungs than in blood. Thesein vitro results reinforce the hypothesis that antimalarial drugs could be effective as an anti-COVID-19 treatment.

Age at diagnosis and health-related quality of life are associated with fatigue in systemic lupus erythematosus patients: Data from the Almenara Lupus Cohort.

To define the factors associated with fatigue in Mestizo patients with Systemic Lupus Erythematosus (SLE). This is a cross-sectional study of SLE patients from a single center cohort. Visits were performed every six months. For these analyses, the first visit between October 2017 and December 2018 was included. Demographic and clinical characteristics as well as treatment were recorded at every visit. Fatigue was ascertained with the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-FT), Health-Related Quality of Life (HRQoL) with the LupusQoL, disease activity with the Systemic Lupus Erythematosus Disease Activity Index -2 K (SLEDAI-2K), and damage with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology damage index (SDI). Prednisone use was recorded as current daily dose. Immunosuppressive drugs and antimalarial use were recorded as current, past or never. Univariable and multivariable analyses were performed using linear regression models. For the multivariable analyses, model selection followed a backward elimination procedure. Two hundred and twenty-six patients were evaluated. The mean (SD) age at diagnosis was 35.6 (13.1) years, 211 (93.4%) were female; and disease duration was 11.0 (7.3) years. The mean SLEDAI and SDI were 2.4 (3.5) and 1.3 (1.5), respectively. The mean FACIT-FT was 33.1 (10.8). On the multivariable analysis, age at diagnosis and some domains of HRQoL (physical health, emotional health and fatigue) remained associated. Age at diagnosis is negatively associated with fatigue whereas HRQoL domains like physical health, emotional health and fatigue are positively associated with fatigue.

Role for antimalarials in the management of COVID-19.

The current review highlights recent insights into direct antiviral effects by antimalarials against severe acute respiratory syndrome (SARS)-CoV-2 and other viruses and their potential indirect effects on the host by avoiding exaggerated immune responses (reduced cytokine release, Toll-like receptor response, antigen presentation related to lysosomal processing). Currently, there is a large debate on the use of antimalarials for prophylaxis and treatment of SARS-CoV-2-induced disease based on preclinical in-vitro data, small case series and extrapolation from earlier studies of their effect on intracellular pathogens, including many viruses. Hydroxychloroquine (HCQ) or chloroquine have not demonstrated robust efficacy in prior randomized controlled studies against several other viruses. In-vitro data indicate a reduced viral replication of SARS-CoV-2. Especially immunomodulatory effects of antimalarials might also contribute to a clinical efficacy. For SARS-CoV-2 various large studies will provide answers as to whether antimalarials have a place in prophylaxis or treatment of the acute virus infection with SARS-CoV-2 but compelling data are missing so far. In-vitro data provide a theoretical framework for an efficacy of antimalarials in SARS-CoV-2-induced disease but clinical proof is currently missing.

Torsades de Pointes in Coronavirus Disease 2019 Infection

A 73-YEAR-OLD MAN (weight 69 kg, height 175 cm) was transferred to the authors’ critical care unit with respiratory and acute renal failure secondary to coronavirus disease 2019 (COVID-19) infection. His past medical history included hypertension, diabetes, and previous stroke, from which he had made a full recovery. The patient was treated with mechanical ventilation and peritoneal dialysis. He was recruited into the hydroxychloroquine arm of the RECOVERY (Randomised Evaluation of COVID-19 Therapy) trial. Baseline electrocardiogram (ECG) and subsequent ECG monitoring were normal and did not demonstrate any QT prolongation. Three days later, the patient developed a ventricular tachycardia with a circulatory collapse. Immediate cardiopulmonary resuscitation was initiated and defibrillator pads attached; however, the arrhythmia self-terminated within 2 minutes (Fig 1). After resuscitation, another ECG showed a normal QT interval. Arterial blood gas analysis did not show any signs of respiratory insufficiency or an acid-base disturbance. There were no signs of myocardial ischemia. A full panel of blood tests was performed, which did not demonstrate any relevant abnormalities in full blood count, biochemical studies, or coagulation. Hypomagnesemia and hypokalemia were absent. Echocardiography was normal. What is the diagnosis? Diagnosis: Torsades de pointes ventricular tachycardia presumably resulting from hydroxychloroquine therapy. Review of the telemetry data demonstrated a polymorphic ventricular tachycardia in the pattern of torsades de pointes, with a spontaneous onset and termination. A cardiac electrophysiology review was requested and confirmed the diagnosis of torsades de pointes. Review of ECGs, blood test results, and medication history allowed the authors to conclude that the arrhythmia had most likely been caused by hydroxychloroquine. Recommendations were made for stringent monitoring of serum electrolytes (to prevent hypomagnesemia and hypokalemia) and daily ECGs. No further antiarrhythmic therapy was recommended at this stage. Hydroxychloroquine was discontinued, and the patient's participation in the RECOVERY trial was terminated. No further arrhythmias were reported during the patent's stay. An adverse drug reaction report was submitted to the UK Medicines and Healthcare products Regulatory Agency (UK MHRA) to register the hydroxychloroquine-related life-threatening arrhythmia. In early 2020 during the COVID-19 pandemic, a number of studies reported possible therapeutic effects of hydroxychloroquine, and it was therefore included as 1 of the drugs in the platform UK RECOVERY trial.1Randomised evalution of COVID-19 Therapy (RECOVERY) Availible at: https://www.recoverytrial.net/files/protocol-archive/recovery-protocol-v4-0-2020-04-14.pdfGoogle Scholar However, preliminary data showed no benefit in hospitalized patients with COVID-19, which led to the UK MHRA instruction to stop recruitment into trials using hydroxychloroquine to treat patients with COVID-19.2UK Medicines & Healthcare products Regulatory AgencyMHRA suspends recruitment to COVID-19 hydroxychloroquine trials.2020https://www.gov.uk/government/news/mhra-suspends-recruitment-to-covid-19-hydroxychloroquine-trialsGoogle Scholar Hydroxychloroquine was introduced in 1955 as an anti-malarial drug. It has immunomodulatory properties that include inhibition of chemotaxis and phagocytosis, reduction of cytokine synthesis, inhibition of phospholipase A2, and signaling in lymphocytes.3Ben-Zvi I Kivity S Langevitz P et al.Hydroxychloroquine: From malaria to autoimmunity.Clin Rev Allerg Immunol. 2012; 42: 145-153Crossref PubMed Scopus (398) Google Scholar,4Kalia S Dutz JP. New concepts in antimalarial use and mode of action in dermatology.Dermatol Ther. 2007; 20: 160-174Crossref PubMed Scopus (187) Google Scholar Hydroxychloroquine has a large spectrum of side effects including cardiomyopathy and arrhythmias associated with the prolongation of the QT interval.3Ben-Zvi I Kivity S Langevitz P et al.Hydroxychloroquine: From malaria to autoimmunity.Clin Rev Allerg Immunol. 2012; 42: 145-153Crossref PubMed Scopus (398) Google Scholar Between 1964 and 2020, the UK MHRA registered 916 patients with adverse drug reactions, of whom 679 were classified as serious and 15 as fatal. The most commonly reported adverse drug reactions involved skin (454 cases) and the nervous system, including eye (285) and gastrointestinal tract (165). Cardiac adverse drug reactions were reported in 48 patients and included myocardial and/or pericardial disorders, arrhythmias, and heart failure.5UK Medicines & Healthcare products Regulatory AgencyInteractive drug analysis profile for hydroxychloroquine.2020https://info.mhra.gov.uk/drug-analysis-profiles/dap.html?drug=./UK_EXTERNAL/NONCOMBINED/UK_NON_000544442035.zip&agency=MHRAGoogle Scholar Cardiac arrhythmias were reported in 18 patients. Anesthesiologists should continue to be aware of the importance of a comprehensive drug history and are reminded of potential life-threatening arrhythmias when hydroxychloroquine is used. We declare that we have no known competing interests or relationships that could have influenced the work reported in this paper.

Chloroquine, Hydroxychloroquine and Hearing Loss: A Study in Systemic Lupus Erythematosus Patients.

Objectives/HypothesisAntimalarial drugs (chloroquine and hydroxychloroquine) are widely used for the treatment of systemic lupus erythematosus (SLE). However, these drugs may have side effects such as hearing loss. This study aimed to describe the hearing function in SLE patients using antimalarials. Secondarily, this study aimed to investigate whether SLE causes hearing loss and if there are any serological or clinical aspects of this diseases associated with inner ear damage.Study DesignCross‐sectional study.MethodsThis study included 84 individuals (43 SLE patients and 41 controls) with audiometry and tympanometry tests. Epidemiological, clinical, serological, and treatment profiles of SLE patients were extracted from the charts.ResultsSLE patients had more sensorineural hearing loss than controls (23.2% vs. 0; P = .001). Pure‐tone averages in SLE patients using antimalarials and not using antimalarials were similar (8.75 vs. 8.75; P = .63). At 8,000 Hz, antimalarial dug nonusers performed worse than users (10.00 vs. 22.50; P = .03). Tympanometry was normal in all participants. SLE serological and clinical profiles in patients with and without hearing loss were the same (all P = nonsignificant).ConclusionsThere is a high prevalence of hearing loss in SLE that is not affected by antimalarial drug use.Level of Evidence3b Laryngoscope, 131:E957–E960, 2021

COVID-19 and dermatology: a comprehensive guide for dermatologists.

Linked articles: COVID‐19 SPECIAL FORUM. J Eur Acad Dermatol Venereol 2020; 34: e291–e310.

FRI0186 JOINT INVOLVEMENT AND DISEASE ACTIVITY IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS: CALCULATION OF SWOLLEN TO TENDER JOINT COUNT RATIO IN A REAL WORLD COHORT IN THE US

Background:Joint swelling and tenderness are common in patients with systemic lupus erythematosus (SLE). Swollen to tender joint count ratio (STR) is an index originally used in rheumatoid arthritis (RA) which assesses severity of disease activity based on 28 joint counts [1]. In RA, STR is a predictor of treatment response with a higher score indicating greater likelihood of responding.Objectives:To characterize SLE patients in a real-world cohort based on disease activity as defined by STR.Methods:The OM1 SLE Registry (OM1, Boston, MA) follows more than 37,000 SLE patients longitudinally with deep clinical data, including laboratory, patient-reported and disease activity information, and linked administrative claims, starting from 2013. Patients ≥16 years of age with swollen and tender joint counts based on 28 joints on the same encounter were included. STRs were calculated by inserting 1 if the denominator was 0 [2]. Patients were categorized by first available STR as having low (STR &lt;0.5), moderate (0.5 ≤ STR ≤ 1.0), and high (STR &gt;1.0) disease activity. Clinical characteristics were summarized by disease activity group. Definitions of SLE treatments were based on 2019 EULAR recommendations [3].Results:As of December 2019, there were 9,919 patients with at least one STR available in the OM1 SLE Registry. STR was low in 80.4%, moderate in 12.2%, and high in 7.4% of patients. Mean age overall was 52.1 years (standard deviation: 14.8), 92.1% were female, and 71.8% of 7,730 patients with known race were white. Clinical characteristics by STR group are described in Table 1. Antimalarial use decreased and immunosuppressant use increased with increasing STR. Use of select disease-modifying antirheumatic drugs (DMARDs) was higher among patients with moderate or high STR. Lupus nephritis was more common in patients with low STR. A higher proportion of patients with moderate STR had osteoarthritis. The proportion of patients with anxiety and depression decreased with increasing STR. On average, patient and physician global assessments from MDHAQ were higher for patients with moderate STR.Table 1.Clinical characteristics of patients with SLE by swollen:tender joint count ratio groupLowSTR &lt;0.5(N=7,970)Moderate0.5 ≤ STR ≤ 1.0(N=1,211)HighSTR &gt;1.0(N=738)Treatment prior to STR, n (%) Antimalarial5,106 (64.1%)702 (58.0%)427 (57.9%) Biologics (belimumab or rituximab)662 (8.3%)113 (9.3%)70 (9.5%) Immunosuppressants2,310 (29.0%)398 (32.9%)252 (34.1%) Select DMARDs635 (8.0%)165 (13.6%)94 (12.7%) Steroids4,437 (55.7%)785 (64.8%)434 (58.8%)Disease conditions prior to STR, n (%) Anxiety266 (3.3%)25 (2.1%)12 (1.6%) Depression1,127 (14.1%)149 (12.3%)80 (10.8%) Lupus nephritis984 (12.3%)117 (9.7%)72 (9.8%) Osteoarthritis2,336 (29.3%)393 (32.5%)193 (26.2%) Osteoporosis631 (7.9%)95 (7.8%)47 (6.4%)MDHAQ, N1,991388230MDHAQ, mean (SD) Patient global assessment (0-10)4.5 (2.9)5.3 (2.7)4.4 (2.8) Physician global assessment (0-10)2.8 (2.7)3.8 (2.6)2.8 (2.3)Conclusion:Differences in treatments received were apparent between patients of varying disease activity groups with trends towards increased use among patients with higher disease activity. Additional research is needed to determine the utility of this measure for assessing SLE-related outcomes.

AB0449 IMPACT OF REMISSION AND LOW DISEASE ACTIVITY (LDA) ON HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) PATIENTS: A SYSTEMATIC LITERATURE REVIEW (SLR)

Background:Treat-to-target strategy has been proposed in SLE. Achieving remission/LDAS should prevent damage, reduce mortality and improve HRQoL.Objectives:To determine the protective value of remission or LDA states on HRQoL in SLE using a SLR.Methods:Two independent reviewers identified studies in Medline and Cochrane library and extracted data on remission, LDA and HRQoL. Remission and LDA definitions included disease activity (SLEDAI and its variants, SLAM and PGA), serological activity, new organ/system, prednisone (PDN) dose (mg/day), immunosuppressives (IS) drugs, antimalarial (AM) use and remission duration. The quality of the studies was assessed with the Newcastle-Otawa Scale (NOS).Results:Three manuscripts (1059 patients) for remission and 4 (2385 patients) for LDA were included (America, Europe &amp; Asia Pacific). All the studies reached seven out of nine NOS points. Remission rates ranged 25-39%; and LDA: 42-62%. Even less stringent remission or LDA definitions predicted/were associated with a better HRQoL. Physical rather than mental domains were more associated with remission or LDA.Table 1.Association between remission and HRQoLAuthorsCountry/RegionPatientsRemissionRemission (%)Domains positively associated or predicted by remissionMok et al*China769SLEDAI=0Serologic= AllowedPGA&lt;0.5PDN ≤ 5IS=YesAM=YesDuration≥5years25.1Remission&gt;5 years vs not on remissionSF-36:Role physical, bodily pain, general health, vitality, social functioning, role emotional, PCS and MCSLupusPRO:Symptoms, medications, procreation, physical health, pain, emotional, image, HRQoL totalTsang-A-Sjoe et al#Netherlands154SLEDAI=0Serologic= allowedPGA ≤2/10PDN ≤ 5IS=YesAM=YesDuration=NR39.0 at baselineRemission on- or off-therapy predicted a better SF-36 PCS but not MCSMargiotta et al*Italy136SLEDAI=0Serologic= allowedPGA= NRPDN ≤ 5IS=YesAM=YesDuration&gt;5 years39.0Remission &gt;5years vs unremitted or remission&lt;5 yearsSF-36:Physical health, role physical, bodily pain, general health, social functioningPCS: Physical component summary. MCS: Mental component summary. *Cross-sectional #LongitudinalTable 2.Association between LDA and HRQoLAuthorsCountry/RegionPatientsLDALDA (%)Domains positively associated or predicted by LDASGolder et al*Asia Pacific1422SLEDAI≤ 4PGA≤ 1PDN ≤ 7.5IS=YesAM=YesNew manifestations: NoDuration=NR42.0SF-36:Role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health, PCS and MCSUgarte-Gil et al#USA483SLAM≤ 3PGA=NRPDN ≤ 7.5IS=NoAM=YesNew manifestations: NRDuration=NRNRSF-36:Physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health, PCS and MCSUgarte-Gil et al#Peru243SLEDAI≤ 4PGA=NRPDN ≤ 7.5IS=YesAM=YesNew manifestations: NRDuration=NR48.6 at baselineLupusQoLPhysical health, pain, planning, burden to others, emotional health, fatiguePoomsalood et al*Thailand237SLEDAI≤ 2Serologic= allowedPGA=NRPDN ≤ 7.5IS=YesAM=YesNew manifestations: NRDuration=NR61.6SLEQoLUnivariable:physical, activities, symptom, treatment, mood, self-image and total.Multivariable: Better global QoLPCS: Physical component summary. MCS: Mental component summary. *Cross-sectional #LongitudinalConclusion:In SLE patients, achieving remission or LDA, is associated with a better HRQoL.Disclosure of Interests:Manuel F. Ugarte-Gil Grant/research support from: Jannsen, Pfizer, Claudia Mendoza Pinto: None declared, Cristina Reategui Sokolova: None declared, Guillermo Pons-Estel Grant/research support from: JANSSEN and GSK, Consultant of: JANNSEN, GSK and SANOFI, Speakers bureau: PFIZER, JANNSEN and GSK, Ronald van Vollenhoven Grant/research support from: AbbVie, Arthrogen, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, GSK, Janssen, Lilly, Medac, Merck, Novartis, Pfizer, Roche, and UCB, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, Graciela S Alarcon: None declared, Bernardo Pons-Estel Grant/research support from: GSK, Janssen, Consultant of: GSK, Janssen, Speakers bureau: GSK, Janssen