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1.
Int J Mol Sci ; 22(16)2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1662665

ABSTRACT

Endometriosis, an estrogen-dependent chronic gynecological disease, is characterized by a systemic inflammation that affects circulating red blood cells (RBC), by reducing anti-oxidant defenses. The aim of this study was to investigate the potential beneficial effects of licorice intake to protect RBCs from dapsone hydroxylamine (DDS-NHOH), a harmful metabolite of dapsone, commonly used in the treatment of many diseases. A control group (CG, n = 12) and a patient group (PG, n = 18) were treated with licorice extract (25 mg/day), for a week. Blood samples before (T0) and after (T1) treatment were analyzed for: i) band 3 tyrosine phosphorylation and high molecular weight aggregates; and ii) glutathionylation and carbonic anhydrase activity, in the presence or absence of adjunctive oxidative stress induced by DDS-NHOH. Results were correlated with plasma glycyrrhetinic acid (GA) concentrations, measured by HPLC-MS. Results showed that licorice intake decreased the level of DDS-NHOH-related oxidative alterations in RBCs, and the reduction was directly correlated with plasma GA concentration. In conclusion, in PG, the inability to counteract oxidative stress is a serious concern in the evaluation of therapeutic approaches. GA, by protecting RBC from oxidative assault, as in dapsone therapy, might be considered as a new potential tool for preventing further switching into severe endometriosis.


Subject(s)
Anti-Infective Agents/adverse effects , Dapsone/adverse effects , Endometriosis/chemically induced , Glycyrrhiza , Plant Extracts/therapeutic use , Protective Agents/therapeutic use , Adult , Antioxidants/therapeutic use , Endometriosis/prevention & control , Erythrocytes/drug effects , Female , Glycyrrhiza/chemistry , Humans , Oxidative Stress/drug effects , Young Adult
2.
Mayo Clin Proc ; 95(6): 1213-1221, 2020 06.
Article in English | MEDLINE | ID: covidwho-1450185

ABSTRACT

As the coronavirus disease 19 (COVID-19) global pandemic rages across the globe, the race to prevent and treat this deadly disease has led to the "off-label" repurposing of drugs such as hydroxychloroquine and lopinavir/ritonavir, which have the potential for unwanted QT-interval prolongation and a risk of drug-induced sudden cardiac death. With the possibility that a considerable proportion of the world's population soon could receive COVID-19 pharmacotherapies with torsadogenic potential for therapy or postexposure prophylaxis, this document serves to help health care professionals mitigate the risk of drug-induced ventricular arrhythmias while minimizing risk of COVID-19 exposure to personnel and conserving the limited supply of personal protective equipment.


Subject(s)
Death, Sudden, Cardiac , Hydroxychloroquine , Long QT Syndrome , Lopinavir , Risk Adjustment/methods , Ritonavir , Torsades de Pointes , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Betacoronavirus/drug effects , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Drug Combinations , Drug Monitoring/methods , Drug Repositioning/ethics , Drug Repositioning/methods , Electrocardiography/methods , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/mortality , Long QT Syndrome/therapy , Lopinavir/administration & dosage , Lopinavir/adverse effects , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Ritonavir/administration & dosage , Ritonavir/adverse effects , SARS-CoV-2 , Torsades de Pointes/chemically induced , Torsades de Pointes/mortality , Torsades de Pointes/therapy
5.
JAMA ; 325(14): 1426-1435, 2021 04 13.
Article in English | MEDLINE | ID: covidwho-1201461

ABSTRACT

Importance: Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. Objective: To determine whether ivermectin is an efficacious treatment for mild COVID-19. Design, Setting, and Participants: Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. Intervention: Patients were randomized to receive ivermectin, 300 µg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). Main Outcomes and Measures: Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. Results: Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). Conclusion and Relevance: Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04405843.


Subject(s)
COVID-19/drug therapy , Ivermectin/therapeutic use , Adult , Aged , Anti-Infective Agents/adverse effects , Double-Blind Method , Drug Administration Schedule , Female , Humans , Ivermectin/adverse effects , Male , Middle Aged , Patient Acuity , SARS-CoV-2/isolation & purification , Time Factors , Treatment Failure
6.
JAMA Netw Open ; 4(4): e216842, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1198342

ABSTRACT

Importance: Critical illness, a marked inflammatory response, and viruses such as SARS-CoV-2 may prolong corrected QT interval (QTc). Objective: To evaluate baseline QTc interval on 12-lead electrocardiograms (ECGs) and ensuing changes among patients with and without COVID-19. Design, Setting, and Participants: This cohort study included 3050 patients aged 18 years and older who underwent SARS-CoV-2 testing and had ECGs at Columbia University Irving Medical Center from March 1 through May 1, 2020. Patients were analyzed by treatment group over 5 days, as follows: hydroxychloroquine with azithromycin, hydroxychloroquine alone, azithromycin alone, and neither hydroxychloroquine nor azithromycin. ECGs were manually analyzed by electrophysiologists masked to COVID-19 status. Multivariable modeling evaluated clinical associations with QTc prolongation from baseline. Exposures: COVID-19, hydroxychloroquine, azithromycin. Main Outcomes and Measures: Mean QTc prolongation, percentage of patients with QTc of 500 milliseconds or greater. Results: A total of 965 patients had more than 2 ECGs and were included in the study, with 561 (58.1%) men, 198 (26.2%) Black patients, and 191 (19.8%) aged 80 years and older. There were 733 patients (76.0%) with COVID-19 and 232 patients (24.0%) without COVID-19. COVID-19 infection was associated with significant mean QTc prolongation from baseline by both 5-day and 2-day multivariable models (5-day, patients with COVID-19: 20.81 [95% CI, 15.29 to 26.33] milliseconds; P < .001; patients without COVID-19: -2.01 [95% CI, -17.31 to 21.32] milliseconds; P = .93; 2-day, patients with COVID-19: 17.40 [95% CI, 12.65 to 22.16] milliseconds; P < .001; patients without COVID-19: 0.11 [95% CI, -12.60 to 12.81] milliseconds; P = .99). COVID-19 infection was independently associated with a modeled mean 27.32 (95% CI, 4.63-43.21) millisecond increase in QTc at 5 days compared with COVID-19-negative status (mean QTc, with COVID-19: 450.45 [95% CI, 441.6 to 459.3] milliseconds; without COVID-19: 423.13 [95% CI, 403.25 to 443.01] milliseconds; P = .01). More patients with COVID-19 not receiving hydroxychloroquine and azithromycin had QTc of 500 milliseconds or greater compared with patients without COVID-19 (34 of 136 [25.0%] vs 17 of 158 [10.8%], P = .002). Multivariable analysis revealed that age 80 years and older compared with those younger than 50 years (mean difference in QTc, 11.91 [SE, 4.69; 95% CI, 2.73 to 21.09]; P = .01), severe chronic kidney disease compared with no chronic kidney disease (mean difference in QTc, 12.20 [SE, 5.26; 95% CI, 1.89 to 22.51; P = .02]), elevated high-sensitivity troponin levels (mean difference in QTc, 5.05 [SE, 1.19; 95% CI, 2.72 to 7.38]; P < .001), and elevated lactate dehydrogenase levels (mean difference in QTc, 5.31 [SE, 2.68; 95% CI, 0.06 to 10.57]; P = .04) were associated with QTc prolongation. Torsades de pointes occurred in 1 patient (0.1%) with COVID-19. Conclusions and Relevance: In this cohort study, COVID-19 infection was independently associated with significant mean QTc prolongation at days 5 and 2 of hospitalization compared with day 0. More patients with COVID-19 had QTc of 500 milliseconds or greater compared with patients without COVID-19.


Subject(s)
Azithromycin , COVID-19 , Electrocardiography , Hydroxychloroquine , Long QT Syndrome , Aged, 80 and over , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19 Testing/methods , Drug Therapy, Combination/methods , Drug Therapy, Combination/statistics & numerical data , Electrocardiography/methods , Electrocardiography/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/epidemiology , Long QT Syndrome/virology , Male , Middle Aged , New York/epidemiology , Outcome and Process Assessment, Health Care , Risk Factors , SARS-CoV-2 , Time Factors
7.
BMJ Case Rep ; 14(3)2021 Mar 24.
Article in English | MEDLINE | ID: covidwho-1150214

ABSTRACT

Hydroxychloroquine has been widely prescribed to treat patients with COVID-19 pneumonia. A 73-year-0ld woman with COVID-19 pneumonia was treated with dexamethasone and hydroxychloroquine. Her home medications, citalopram and donepezil, were continued. The ECG prior to starting hydroxychloroquine showed normal sinus rhythm with prolonged corrected QT (QTc) of 497 ms, due to citalopram and donepezil therapy. Repeat ECG on days 3 and 4 of hydroxychloroquine therapy showed significantly prolonged QTc of 557 ms and 538 ms, respectively, despite normal serum electrolytes. All QT-prolonging medications including hydroxychloroquine were discontinued on day 4; however, she suffered a transient torsades de pointes lasting for about 15 s, which resolved before any intervention. QTc improved to 477 ms, after discontinuation of QT-prolonging medications. The patient had QTc prolongation and torsades de pointes due to therapy with multiple QT-prolonging medications. Medicine reconciliation and careful monitoring of QTc may help prevent cardiac complications in patients with COVID-19 treated with hydroxychloroquine.


Subject(s)
COVID-19/drug therapy , Dexamethasone/adverse effects , Hydroxychloroquine/adverse effects , Torsades de Pointes/chemically induced , Aged , Anti-Infective Agents/adverse effects , Anti-Infective Agents/therapeutic use , Citalopram/adverse effects , Citalopram/therapeutic use , Dexamethasone/therapeutic use , Donepezil/adverse effects , Donepezil/therapeutic use , Drug Therapy, Combination , Electrocardiography/methods , Female , Heart Diseases/chemically induced , Heart Diseases/prevention & control , Humans , Hydroxychloroquine/therapeutic use , Long QT Syndrome/chemically induced , SARS-CoV-2
8.
Anatol J Cardiol ; 25(3): 184-190, 2021 03.
Article in English | MEDLINE | ID: covidwho-1125300

ABSTRACT

OBJECTIVE: The effects of treatment of coronavirus disease 2019 (COVID-19) with a triple combination composed of hydroxychloroquine, an an-tiviral, and an antibiotic on electrocardiography (ECG) parameters in patients with mild-to-moderate symptoms are not wholly understood. We aimed to explore the changes in ECG parameters after treatment with triple combination therapy in patients with mild-to-moderate symptomatic COVID-19. METHODS: This retrospective, single-center case series analyzed 91 patients with mild-to-moderate symptomatic COVID-19 at Ankara Gazi Mus-tafa Kemal State Hospital of Ankara City, Turkey, from April 1, 2020, to April 30, 2020. Forty-three patients were treated with hydroxychloroquine+oseltamivir+azithromycin (Group 1) and 48 patients were treated with hydroxychloroquine+oseltamivir+levofloxacin (Group 2). Heart rate, P wave duration, P wave dispersion, PR interval, QRS duration, corrected QT interval (QTc), QTc dispersion (QTD), delta QTc, Tp-e, Tp-e dispersion, and Tp-e/QTc ratio were all calculated from the baseline and posttreatment 12-lead ECG recordings. RESULTS: The QTc, QRS duration, Tp-e, PR interval, and P wave duration were significantly increased after treatment (p<0.001; p<0.001; p<0.001; p=0.001; p=0.001). The posttreatment C-reactive protein level was significantly lower than at baseline in Group 1 (p=0.014). At admission, 30% of patients had QT prolongation, and 4.3% of them had a QT duration >500 ms. Both Group 1 and Group 2 showed significant prolongation of the QTc interval (Group 1; p<0.001 vs. Group 2; p<0.001), QRS duration (Group 1; p=0.006 vs. Group 2; p=0.014), Tp-e (Group 1; p=0.036 vs. Group 2; p<0.001), and PR interval (Group 1; p=0.002 vs. Group2; p=0.05). The QTD was significantly decreased in Group 1 (p<0.001). None of the patients experienced any overt ventricular arrhythmia. CONCLUSION: To the best of our knowledge, this study is the first to investigate QT prolongation in a population of COVID-19 patients treated with triple combination therapy. We found that there was a significant decrease in the QTD after the treatment in patients who were taking triple therapy including azithromycin.


Subject(s)
COVID-19/drug therapy , Long QT Syndrome/chemically induced , SARS-CoV-2 , Adolescent , Adult , Aged , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , COVID-19/pathology , Drug Therapy, Combination , Electrocardiography , Female , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Levofloxacin/administration & dosage , Levofloxacin/adverse effects , Long QT Syndrome/physiopathology , Male , Middle Aged , Oseltamivir/administration & dosage , Oseltamivir/adverse effects , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Young Adult
9.
Eur J Pharmacol ; 898: 173934, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1086916

ABSTRACT

Metformin is the most commonly prescribed oral antidiabetic medication. Direct/indirect activation of Adenosine Monophosphate-activated protein kinase (AMPK) and non-AMPK pathways, amongst others, are deemed to explain the molecular mechanisms of action of metformin. Metformin is an established insulin receptor sensitising antihyperglycemic agent, is highly affordable, and has superior safety and efficacy profiles. Emerging experimental and clinical evidence suggests that metformin has pleiotropic non-glycemic effects. Metformin appears to have weight stabilising, renoprotective, neuroprotective, cardio-vascular protective, and antineoplastic effects and mitigates polycystic ovarian syndrome. Anti-inflammatory and antioxidant effects of metformin seem to qualify it as an adjunct therapy in treating infectious diseases such as tuberculosis, viral hepatitis, and the current novel Covid-19 infections. So far, metformin is the only prescription medicine relevant to the emerging field of senotherapeutics. Non-glycemic effects of metformin favourable to its repurposing in therapeutic use are hereby discussed.


Subject(s)
Anti-Infective Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Hypoglycemic Agents/therapeutic use , Immunologic Factors/therapeutic use , Metformin/therapeutic use , Protective Agents/therapeutic use , Animals , Anti-Infective Agents/adverse effects , Antineoplastic Agents/adverse effects , COVID-19/drug therapy , COVID-19/epidemiology , Cardiovascular Diseases/prevention & control , Female , Humans , Hypoglycemic Agents/adverse effects , Immunologic Factors/adverse effects , Kidney Diseases/prevention & control , Metabolic Syndrome/drug therapy , Metformin/adverse effects , Obesity/drug therapy , Pandemics , Polycystic Ovary Syndrome/drug therapy , Protective Agents/adverse effects , SARS-CoV-2
10.
Int J Risk Saf Med ; 32(1): 3-17, 2021.
Article in English | MEDLINE | ID: covidwho-1058394

ABSTRACT

Coronavirus disease 2019 (COVID-19) is a viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) presenting with pulmonary and extra-pulmonary manifestations. The first case was reported in Wuhan, China in December 2019 and it has rapidly progressed to the form of a pandemic. The presentation is mild in about 80 percent of the cases but the disease can also progress to a severe form of respiratory illness leading to acute respiratory distress syndrome (ARDS) and sometimes multi-organ failure, especially in people with other co-morbidities. Pregnant women also appear to be at a greater risk of acquiring a severe infection due to physiological changes during pregnancy. Many drugs with in vitro activity against the virus or an immunomodulatory effect have been considered for repurposing or have been tried as off-label drugs. The safety data regarding the use of newly approved or off-label or investigational drugs in pregnant women is limited and this poses a great challenge for clinicians. Therefore, it is important to know the utility and safety of the medications to avoid untoward adverse effects on pregnant women and fetuses. In this review, we aim to provide an overview of the approved, off-label, unlicensed, new and some promising pharmacological options for their use in the treatment of COVID-19 and the safety profile in pregnancy in an Indian scenario.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Fetus/drug effects , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Anti-Infective Agents/adverse effects , Anti-Infective Agents/therapeutic use , Antiviral Agents/adverse effects , COVID-19/epidemiology , Drugs, Investigational , Female , Humans , Hydroxychloroquine/adverse effects , Hydroxychloroquine/therapeutic use , India/epidemiology , Off-Label Use , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnant Women , SARS-CoV-2 , Steroids/adverse effects , Steroids/therapeutic use
11.
N Engl J Med ; 384(5): 417-427, 2021 02 04.
Article in English | MEDLINE | ID: covidwho-963653

ABSTRACT

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. METHODS: We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).


Subject(s)
Anti-Infective Agents/therapeutic use , COVID-19/prevention & control , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Adult , Anti-Infective Agents/adverse effects , COVID-19/transmission , COVID-19/virology , Disease Transmission, Infectious/prevention & control , Double-Blind Method , Female , Humans , Hydroxychloroquine/adverse effects , Male , Middle Aged , Patient Compliance , Treatment Failure , Viral Load
12.
Cochrane Database Syst Rev ; 9: CD013626, 2020 09 16.
Article in English | MEDLINE | ID: covidwho-959059

ABSTRACT

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. If the mouth and nose of HCWs are irrigated with antimicrobial solutions, this may help reduce the risk of active infection being passed from infected patients to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves, or alterations in the natural microbial flora of the mouth or nose. Understanding these possible side effects is particularly important when the HCWs are otherwise fit and well. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays used by healthcare workers (HCWs) to protect themselves when treating patients with suspected or confirmed COVID-19 infection. SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020.  SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed randomised controlled trials (RCTs). We therefore planned to include the following types of studies: RCTs; quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies.   We sought studies comparing any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to HCWs, with or without the same intervention being given to the patients with COVID-19. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) viral content of aerosol, when present (if intervention administered to patients); 4) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 5) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We found no completed studies to include in this review. We identified three ongoing studies (including two RCTs), which aim to enrol nearly 700 participants. The interventions included in these trials are povidone iodine, nitric oxide and GLS-1200 oral spray (the constituent of this spray is unclear and may not be antimicrobial in nature).   AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review. This is not surprising given the relatively recent emergence of COVID-19 infection. It is promising that the question posed in this review is being addressed by two RCTs and a non-randomised study. We are concerned that only one of the ongoing studies specifically states that it will evaluate adverse events and it is not clear if this will include changes in the sense of smell or to the oral and nasal microbiota, and any consequences thereof. Very few interventions have large and dramatic effect sizes. If a positive treatment effect is demonstrated when studies are available for inclusion in this review, it may not be large. In these circumstances in particular, where those receiving the intervention are otherwise fit and well, it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.


Subject(s)
Anti-Infective Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/transmission , Health Personnel , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Mouthwashes/administration & dosage , Nasal Sprays , Pneumonia, Viral/transmission , Anti-Infective Agents/adverse effects , COVID-19 , Coronavirus Infections/prevention & control , Humans , Mouth/virology , Mouthwashes/adverse effects , Nose/virology , Occupational Diseases/etiology , Occupational Diseases/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , SARS-CoV-2 , Therapeutic Irrigation
14.
BMJ Case Rep ; 13(8)2020 Aug 24.
Article in English | MEDLINE | ID: covidwho-827667

ABSTRACT

Methaemoglobinaemia is a rare disease that is typically caused by a medication or other exogenous agent, with dapsone being the most common. It occurs when the concentration of methaemoglobin rises via ferrous haeme irons becoming oxidised to the ferric state, which shifts the oxygen dissociation curve to the left. The net result of an elevated methaemoglobin concentration is functional anaemia and impaired oxygen delivery to tissues. At lower blood levels, this can cause symptoms such as cyanosis, lethargy, headache and fatigue, whereas at higher levels it can be fatal. Here we discuss a subtle case of dapsone-induced methaemoglobinaemia presenting as subacute mental status changes and apparent hypoxia, thus highlighting the association between methaemoglobinaemia and dapsone. This case demonstrates the importance of thorough medication reconciliation and maintaining a broad differential diagnosis, while also recognising the significance of conflicting data and their implications for the workup.


Subject(s)
Anti-Infective Agents/adverse effects , Dapsone/adverse effects , Methemoglobinemia , Aged , Confusion/chemically induced , Female , Humans , Memory Disorders/chemically induced , Methemoglobin/analysis , Methemoglobinemia/chemically induced , Methemoglobinemia/diagnosis , Oxygen/blood
16.
Expert Rev Clin Pharmacol ; 13(11): 1183-1190, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-811405

ABSTRACT

INTRODUCTION: Patients with moderate to severe COVID-19 infection require specific drugs to prevent the morbidity and mortality. Hydroxychloroquine (HCQ) has shown some promise in the management of COVID 19. Minocycline, because of its anticytokine and other useful properties can be an ideal candidate for combining with HCQ. AREAS COVERED: Here we review the need and mechanisms and reasons for combining HCQ and minocycline moderate to severe COVID-19 infection. We also reviewed the advantages, potential safety concerns and precautions to be taken, while combining HCQ and minocycline. EXPERT OPINION: Combining HCQ and minocycline offers many advantages in the management of moderate to severe COVID-19 infection. Both drugs are cheaper, widely available and long-term safety data and contraindications are well known. We do not recommend this combination for prophylaxis or use in asymptomatic or mild disease patients as this can lead to unnecessary safety concerns. Additive antimicrobial and anticytokine effects of both drugs may reduce the morbidity and mortality among patients with COVID-19 and may act as a cheaper alternative to the costlier drugs, however, thorough clinical research is warranted. We call upon public and private healthcare bodies to come up with large well-designed clinical studies for generating evidence-based recommendations.


Subject(s)
Coronavirus Infections/drug therapy , Hydroxychloroquine/administration & dosage , Minocycline/administration & dosage , Pneumonia, Viral/drug therapy , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , COVID-19 , Coronavirus Infections/physiopathology , Drug Therapy, Combination , Humans , Hydroxychloroquine/adverse effects , Minocycline/adverse effects , Pandemics , Pneumonia, Viral/physiopathology , Severity of Illness Index
17.
Cochrane Database Syst Rev ; 9: CD013627, 2020 09 16.
Article in English | MEDLINE | ID: covidwho-791634

ABSTRACT

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. If the mouth and nose of patients with infection are irrigated with antimicrobial solutions, this may help the patients by killing any coronavirus present at those sites. It may also reduce the risk of the active infection being passed to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves or alterations in the natural microbial flora of the mouth or nose. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to both the patients and the HCWs caring for them. SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020.  SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed RCTs. We therefore planned to include the following types of studies: randomised controlled trials (RCTs); quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies.   We sought studies comparing antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered with any frequency or dosage to suspected/confirmed COVID-19 patients. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) RECOVERY* (www.recoverytrial.net) outcomes in patients (mortality; hospitalisation status; use of ventilation; use of renal dialysis or haemofiltration); 2) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 3) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 4) change in COVID-19 viral load in patients; 5) COVID-19 viral content of aerosol (when present); 6) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 7) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We found no completed studies to include in this review. We identified 16 ongoing studies (including 14 RCTs), which aim to enrol nearly 1250 participants. The interventions included in these trials are ArtemiC (artemisinin, curcumin, frankincense and vitamin C), Citrox (a bioflavonoid), cetylpyridinium chloride, chlorhexidine, chlorine dioxide, essential oils, hydrogen peroxide, hypertonic saline, Kerecis spray (omega 3 viruxide - containing neem oil and St John's wort), neem extract, nitric oxide releasing solution, povidone iodine and saline with baby shampoo.  AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review. This is not surprising given the relatively recent emergence of COVID-19 infection. It is promising that the question posed in this review is being addressed by a number of RCTs and other studies. We are concerned that few of the ongoing studies specifically state that they will evaluate adverse events such as changes in the sense of smell or to the oral and nasal microbiota, and any consequences thereof. Very few interventions have large and dramatic effect sizes. If a positive treatment effect is demonstrated when studies are available for inclusion in this review, it may not be large. In these circumstances in particular it may be a challenge to weigh up the benefits against the harms if the latter are of uncertain frequency and severity.


Subject(s)
Anti-Infective Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/therapy , Health Personnel , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Mouthwashes/administration & dosage , Nasal Sprays , Pneumonia, Viral/therapy , Anti-Infective Agents/adverse effects , COVID-19 , Coronavirus Infections/prevention & control , Coronavirus Infections/transmission , Humans , Mouth/virology , Mouthwashes/adverse effects , Nose/virology , Occupational Diseases/etiology , Occupational Diseases/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/transmission , SARS-CoV-2 , Therapeutic Irrigation
18.
Cochrane Database Syst Rev ; 9: CD013628, 2020 09 16.
Article in English | MEDLINE | ID: covidwho-774574

ABSTRACT

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. The risks of transmission of infection are greater when a patient is undergoing an aerosol-generating procedure (AGP). Not all those with COVID-19 infection are symptomatic, or suspected of harbouring the infection. If a patient who is not known to have or suspected of having COVID-19 infection is to undergo an AGP, it would nonetheless be sensible to minimise the risk to those HCWs treating them. If the mouth and nose of an individual undergoing an AGP are irrigated with antimicrobial solutions, this may be a simple and safe method of reducing the risk of any covert infection being passed to HCWs through droplet transmission or direct contact. Alternatively, the use of antimicrobial solutions by the HCW may decrease the chance of them acquiring COVID-19 infection. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves or alterations in the natural microbial flora of the mouth or nose. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to HCWs and/or patients when undertaking AGPs on patients without suspected or confirmed COVID-19 infection. SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020.  SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed RCTs. We therefore planned to include the following types of studies: randomised controlled trials (RCTs); quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies.   We sought studies comparing any antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered to the patient or HCW before and/or after an AGP. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) incidence of symptomatic or test-positive COVID-19 infection in HCWs or patients; 2) significant adverse event: anosmia (or disturbance in sense of smell). Our secondary outcomes were: 3) COVID-19 viral content of aerosol (when present); 4) change in COVID-19 viral load at site(s) of irrigation; 5) other adverse events: changes in microbiome in oral cavity, nasal cavity, oro- or nasopharynx; 6) other adverse events: allergy, irritation/burning of nasal, oral or oropharyngeal mucosa (e.g. erosions, ulcers, bleeding), long-term staining of mucous membranes or teeth, accidental ingestion. We planned to use GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We found no completed studies to include in this review.   AUTHORS' CONCLUSIONS: We identified no studies for inclusion in this review, nor any ongoing studies. The absence of completed studies is not surprising given the relatively recent emergence of COVID-19 infection. However, we are disappointed that this important clinical question is not being addressed by ongoing studies.


Subject(s)
Anti-Infective Agents/administration & dosage , Betacoronavirus , Coronavirus Infections/transmission , Health Personnel , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Mouthwashes/administration & dosage , Nasal Sprays , Pneumonia, Viral/transmission , Administration, Intranasal , Air Microbiology , Anti-Infective Agents/adverse effects , Asymptomatic Infections/therapy , COVID-19 , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Humans , Mouth/virology , Mouthwashes/adverse effects , Nose/virology , Occupational Diseases/etiology , Occupational Diseases/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Pneumonia, Viral/therapy , SARS-CoV-2
19.
Cardiol Young ; 30(10): 1482-1485, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-669227

ABSTRACT

INTRODUCTION AND AIM: Hydroxychloroquine alone or in combination with azithromycin has been increasingly used for patients with coronavirus disease 2019, in both children and adults. Drugs are generally well tolerated in clinical practice; however, both can cause corrected QT prolongation. We aimed to report our experience of QT interval evaluation associated with the use of hydroxychloroquine with concurrent azithromycin among children testing positive for coronavirus disease 2019. METHODS: Our single-centre; retrospective, study evaluated children with coronavirus disease 2019 disease admitted to the Pediatric Department at Sancaktepe Training and Research Hospital Istanbul, Turkey from 10 March, 2020 to 10 April, 2020. The data including demographics, clinical symptoms, co-morbid diseases, laboratory, radiological findings as well as electrocardiographs of the patients were obtained from our records. Electrocardiograms were evaluated before, one day after and at the termination of the treatment. RESULTS: 21 patients aged 9 to 18 years were evaluated. The median age was 170 months (range 112-214), 51.1% of them were girls and 48.9% were boys. Their laboratory results did not reveal any abnormalities. None of them needed intensive care. We did not detect QT prolongation during or at the termination of the treatment. CONCLUSION: We did not detect QT prolongation during or at the termination of the treatment in our patients due to the fact that they were not severely affected by the disease. Patients were treated in our inpatient clinic and none of them required intensive care. Laboratory results were also insignificant. Furthermore, they did not need other medications.


Subject(s)
Azithromycin , Coronavirus Infections/drug therapy , Electrocardiography/methods , Hydroxychloroquine , Long QT Syndrome , Pneumonia, Viral/drug therapy , Adolescent , Anti-Infective Agents/administration & dosage , Anti-Infective Agents/adverse effects , Azithromycin/administration & dosage , Azithromycin/adverse effects , COVID-19 , Child , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Female , Hospitalization/statistics & numerical data , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/adverse effects , Long QT Syndrome/chemically induced , Long QT Syndrome/diagnosis , Long QT Syndrome/prevention & control , Male , Outcome and Process Assessment, Health Care , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Retrospective Studies , Turkey/epidemiology
20.
Biomed Pharmacother ; 129: 110404, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-622542

ABSTRACT

Nicotine is perhaps the most important and potent, pharmacologically active substance in tobacco products. This commentary examines the possible effects that nicotine has on microbial viability and also on the host's immune system as it responds to the indigenous microflora (the microbiome) due to nicotine-induced changes to the indigenous microbial environment and any associated antigenic stimulation / immunization that may occur. To our knowledge, the analysis of such profound microbiologic changes attributable to a tobacco-related product, such as nicotine, has not been fully explored in the context of its consequences on the viability of the microbiome/microbiota and on some of the host's basic physiologic processes, such as the immune response, and its possible association on the induction and persistence of certain immunologically related diseases. Future studies should be aimed at uncovering the molecular mechanisms involved in such interactions, especially in the context of manipulating them for therapeutic purposes.


Subject(s)
Anti-Infective Agents/therapeutic use , Immune System/drug effects , Immunologic Factors/therapeutic use , Microbiota/drug effects , Nicotine/therapeutic use , Nicotinic Agonists/therapeutic use , Animals , Anti-Infective Agents/adverse effects , Dysbiosis , Host-Pathogen Interactions , Humans , Immune System/immunology , Immunologic Factors/adverse effects , Nicotine/adverse effects , Nicotinic Agonists/adverse effects
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