scholarly journals I. Cloroquina / hidroxicloroquina y azitromicina. Revisión narrativa de seguridad

2020 ◽  
Vol 2 (2) ◽  
pp. 71-82
Author(s):  
Raquel Herrera Comoglio
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Scientific Evidence ◽  
Safety Information ◽  
Torsades De Pointes ◽  
Pharmacovigilance System ◽  
Qtc Interval ◽  
Number Of Patients ◽  
Hospital Patients ◽  
Repurposed Drugs

The SARS-Co-2 pandemic is affecting millions of people, producing hundreds of thousands of deaths, and collapsing healthcare systems worldwide. Due to the lack of specific treatments, repurposed drugs are routinely used in in-hospital patients, though there is no sound-based scientific evidence. The quinine derivatives chloroquine (CQ) and hydroxychloroquine (HCQ) —used as antimalarials, and in autoimmune diseases—, and the antibiotic macrolide azithromycin have been proposed as possible therapies against the SARS-CoV-2 infection and COVID-19. Shortly after this outbreak began, many clinical trials have been registered to evaluate the efficacy of CQ/HCQ, alone or combined with azithromycin, in the treatment of COVID-19 or the prevention of SARS-CoV-2 infection. In the meantime, media information about the possible use of these drugs, politic leaders’ statements and further decisions concerning their efficacy soared public expectations. Both CQ/HCQ and azithromycin are relatively inexpensive and can be administered orally; adverse effects are known at doses used in approved indications. However, their use in a much more significant number of patients increases the risk of occurrence of adverse events. Notably, the potential of both drugs to prolong QTc interval raises concerns about the potentiality to lead to fatal arrhythmias, including torsades de pointes (TdP). The potential blood-glucose-lowering effect of CQ/HCQ could also produce serious adverse effects. The Spanish Pharmacovigilance system has received six cases of serious neuropsychiatric adverse reactions.This narrative review presents a summary of safety information of CQ/HCQ in approved indications, and the emerging experience of their use in the SARS-CoV-2 infection and COVID-19. With randomised clinical trials’ results not available yet, to May 20th 2020, the evidence of efficacy and effectiveness of CQ/HCQ do not suggest a benefit of this use as a treatment of COVID-19. For these purposes, CQ/HCQ alone or in combination with azithromycin should be used only in clinical trials.

scholarly journals Treatment-emergent hypomania possibly associated with over-the-counter supplements

2017 ◽  
Vol 7 (4) ◽  
pp. 160-163
Author(s):  
William Olsufka ◽  
Mary-Ann Abraham
Keyword(s):  
Adverse Effects ◽  
Alternative Medicine ◽  
Complementary And Alternative Medicine ◽  
Safety Profile ◽  
General Public ◽  
Scientific Evidence ◽  
Western World ◽  
Over The Counter ◽  
Treatment Of Depression ◽  
Number Of Patients

Abstract The use of complementary and alternative medicine (CAM) is gaining popularity in the Western world. Among the general public, CAM is often perceived to be associated with less stigma, fewer adverse effects, and may be more affordable. A number of patients utilize CAM for the treatment of depression; however, as there is limited scientific evidence, the safety profile of these supplements are largely unknown. In this case, a 42-year-old man developed hypomania approximately 1 week after S-adenosylmethionine (SAMe) and 5-hydroxytryptophan (5-HTP) therapy was initiated for depression. The combination of SAMe and 5-HTP can potentially induce hypomanic episodes.

scholarly journals Short-Term Effectiveness and Safety of Biologics and Small Molecule Drugs for Moderate to Severe Atopic Dermatitis: A Systematic Review and Network Meta-Analysis

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 927
Author(s):  
José-Juan Pereyra-Rodriguez ◽  
Sara Alcantara-Luna ◽  
Javier Domínguez-Cruz ◽  
Manuel Galán-Gutiérrez ◽  
Ricardo Ruiz-Villaverde ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Atopic Dermatitis ◽  
Adverse Effects ◽  
Small Molecules ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Severe Atopic Dermatitis ◽  
Cochrane Central Register ◽  
Number Of Patients

Background: Some Network Meta-analysis (NMA) has been published regarding atopic dermatitis (AD). These studies have considered drugs under investigation both in monotheraphy or in combination with topical corticosteroids, as well as systemic immunosuppressant therapies. The objective of this study is to evaluate the efficacy and safety of biological agents and small molecules in AD. Methods: A systematic review and NMA of biologics agents and small molecules in AD was performed. A literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for clinical trials and systematic reviews between January 2000 and 19 December 2020. Only randomized clinical trials (RCTs) were included. It was limited to English language and adult human subjects. Two networks were evaluated: monotherapy and combination with TCS. The two primary outcomes were Eczema Area and Severity Index (EASI) 75 and EASI 90 change from baseline to week 12–16, depending on source study cut-off. The Cochrane’s Risk of Bias tool 2011 update was used to analyze the risk of bias, focused on the primary objectives. Results: 30 RCTs (included in 26 publications) were included in the systematic review. Finally, 23 RCTs were included in the quantitative analysis (14 RCTs including 3582 patients in monotherapy; and 9 RCTs including 3686 patients with TCS). In monotherapy, a higher percentage of patients achieving EASI-75 was obtained with Upadacitinib 30 mg [OR: 18.90 (13.94; 25.62)] followed by Abrocitinib 200 mg [OR = 11.26 (7.02; 18.05)] and Upadacitinib 15 mg [OR: 10.89 (8.13; 14.59)]. These results were also observed in studies where the use of topical corticosteroid (TCS) was allowed (OR Upadacitinib 30 mg = 9.43; OR Abrocitinib 200 mg = 6.12; OR Upadacitinib 15 mg = 5.20). Regarding IGA, the percentage of patients achieving IGA0/1 was higher with both doses of Upadacitinib 30 mg [OR: 19.13 (13.14; 27.85)] and 15 mg [OR = 10.95 (7.52; 15.94). In studies where the use of TCS were allowed, however, the dose of Abrocitinib 200 mg [OR = 6.10 (3.94; 9.44)] showed higher efficacy than Upadacitinib 15 mg [OR = 5.47 (3.57; 8.41)]. Regarding safety, the drugs with the highest probability of presenting adverse effects were the Janus kinases (JAK) inhibitors, Upadacitinib and Abrocitinib in monotherapy and Baricitinib in combination with TCS. Discussion: Some risks of bias have been found, which must be taken into account when interpreting the results. The funnel plot shows a possible publication bias that may underestimate the efficacy of drugs. Upadacitinib and Abrocitinib are the drugs with the highest efficacy, both in monotherapy and in association with TCS. However, they were also those associated with the highest risk of adverse effects, showing monoclonal antibodies better safety profile. Limitations: We have included molecules still in the development phase as well studies completed and presented at conferences and with data available in Trialsgov® but not published yet. Several molecules’ development had included a small number of patients from 12 to 17 years of age, without being able to differentiate the results from the adult population. Other: Founding: None. PROSPERO database registration number CRD42021225793.

scholarly journals Energy Drink-Associated Electrophysiological and Ischemic Abnormalities: A Narrative Review

2021 ◽  
Vol 8 ◽  
Author(s):  
Diana X. Cao ◽  
Kimberly Maiton ◽  
Javed M. Nasir ◽  
N. A. Mark Estes ◽  
Sachin A. Shah
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Case Reports ◽  
Fatal Outcome ◽  
Energy Drink ◽  
Supraventricular Arrhythmia ◽  
Significant Finding ◽  
Qtc Interval ◽  
Available Energy ◽  
Energy Drink Consumption

An increasing number of cardiovascular adverse effects, emergency room visits, and deaths have been linked to energy drinks. In this review, we summarized available published literature assessing electrophysiological and ischemic adverse effects associated with energy drink consumption. Overall, 32 case reports and 19 clinical trials are included in this review. Ventricular arrhythmia, supraventricular arrhythmia, and myocardial ischemia were amongst the most commonly reported in case reports with 3 having a fatal outcome. Although serious ischemic changes, arrhythmias, or death were not observed in clinical trials, significant electrophysiological changes, such as PR/PQ interval shortening/prolongation, QT/QTc shortening/prolongation, and ST-T changes, were noted. QT/QTc interval prolongation appears to be the most significant finding in clinical trials, and there appears to be a dose-response relationship between energy drink consumption and QTc prolongation. The exact mechanisms and the particular combination of ingredients behind energy drink-induced cardiac abnormalities require further evaluation. Until more information is available, energy drink use should be considered as part of the differential diagnosis in appropriate patients presenting with electrocardiographic changes. Further, certain patient populations should exercise caution and limit their energy drink consumption.

Potential of Mirabegron and its Extended-release Formulations for the Treatment of Overactive Bladder Syndrome

2020 ◽  
Vol 21 (2) ◽  
pp. 79-88 ◽  
Author(s):  
Pankaj Mandpe ◽  
Bala Prabhakar ◽  
Pravin Shende
Keyword(s):  
Clinical Trials ◽  
Overactive Bladder ◽  
Adverse Effects ◽  
Symptomatic Relief ◽  
Phase Iii ◽  
Overactive Bladder Syndrome ◽  
Modified Release ◽  
Blurred Vision ◽  
Antimuscarinic Drugs ◽  
Tablet Dosage

Background: Overactive bladder syndrome is a broadly occurring urological disorder with a distressing impact on the quality of life. The commonly used antimuscarinic drugs show poor patient compliance because of unsatisfactory potency, tolerability and high occurrence of adverse effects such as dry mouth, blurred vision, constipation, dizziness etc. Mirabegron is the first approved β3-adrenoreceptor agonist, used as mono or in combination therapies for overactive bladder syndrome. Objective: The present review provides an insight into the mechanism, pharmacokinetics, toxicokinetics, clinical trials and the development of various conventional and modified-release dosage forms of mirabegron for the treatment of overactive bladder syndrome. Results: The clinical trials of phase II and phase III of mirabegron demonstrated symptomatic relief from the overactive bladder without disturbing the micturition cycle. To date, mirabegron showed promising results for safety, tolerability and efficacy in patients with overactive bladder syndrome. The modified-release tablet dosage form of mirabegron appear to be a proficient and suitable replacement for antimuscarinics and revealed the tremendous potential to overcome the adverse effects of conventional antimuscarinic drugs like Oxybutyline chloride ER, Detrol LA, VESIcare, etc. Conclusion: Mirabegron shows a distinct mode of action, i.e., targeting β3-adrenoreceptors and improving bladder storage without altering void contractions. The limited side effects, high safety, efficacy and tolerability of mirabegron present an adequate substitute to antimuscarinics. However, long-term analysis and clinical studies are prerequisites for assessing the safety, tolerability and efficacy profile of mirabegron.

Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going?

2020 ◽  
Vol 15 (3) ◽  
pp. 216-233 ◽  
Author(s):  
Maliha Naseer ◽  
Shiva Poola ◽  
Syed Ali ◽  
Sami Samiullah ◽  
Veysel Tahan
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Clinical Trials ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adverse Effects ◽  
Bowel Disease ◽  
Relapse Prevention ◽  
Remission Induction ◽  
Inflammatory Bowel

The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn’s disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms “prebiotics AND ulcerative colitis”, “probiotics AND ulcerative colitis”, “prebiotics AND Crohn's disease”, “probiotics AND Crohn's disease”, “probiotics AND acute pouchitis”, “probiotics AND chronic pouchitis” and “prebiotics AND pouchitis”. Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.

Where Disagreements Can Lie

2018 ◽  
Author(s):  
Inmaculada de Melo-Martín ◽  
Kristen Intemann
Keyword(s):  
Adverse Effects ◽  
Empirical Evidence ◽  
Significant Role ◽  
Scientific Evidence ◽  
Shared Values ◽  
Policy Decisions

Chapter 10 proposes a second recommendation to deal with the negative adverse effects that normatively inappropriate dissent (NID) can have: it calls for a recognition of the limits of scientific evidence when it comes to public policymaking and for an increased focus on potential differences in the values that underlie policy decisions. It contends that while confusion and doubt about the existing empirical evidence or about its strength can contribute to stalled policies, disagreements about values can also play a significant role. Such disagreements can involve what people take to be valuable, how to interpret shared values, how to weigh conflicting values, and what policies are better for promoting certain valuable goals.

The Use of Methotrexate in Rheumatoid Arthritis

1985 ◽  
Vol 19 (5) ◽  
pp. 349-358 ◽  
Author(s):  
Peter W. Letendre ◽  
Douglas J. DeJong ◽  
Donald R. Miller
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Trials ◽  
Folic Acid ◽  
Side Effects ◽  
Adverse Effects ◽  
Systemic Administration ◽  
Refractory Disease ◽  
Controlled Clinical Trials ◽  
Folic Acid Antagonist ◽  
Acid Antagonist

The use of methotrexate in rheumatoid arthritis is reviewed. Methotrexate, a folic acid antagonist, is sometimes employed in an attempt to symptomatically control patients whose disease does not respond adequately to conventional therapies. Systemic administration of 7.5–15 mg/wk in a “pulse” fashion appears to be effective without precipitating severe adverse effects. However, concern over potentially serious side effects and a lack of well-controlled clinical trials have limited its use to severe, refractory disease. Further studies are needed before its role in rheumatoid arthritis can justifiably be expanded.

The Assessment of Ventricular Arrhythmia Indicators Based on Electrocardiography in Patients With Differentiated Thyroid Cancer Followed Up With Levothyroxine Suppression

Angiology ◽  
2021 ◽  
pp. 000331972199334
Author(s):  
Sema Hepsen ◽  
Davut Sakiz ◽  
Hilal Erken Pamukcu ◽  
Ismail Emre Arslan ◽  
Hakan Duger ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Thyroid Cancer ◽  
Ventricular Arrhythmia ◽  
Differentiated Thyroid Cancer ◽  
Linear Regression Analysis ◽  
Male Gender ◽  
Qtc Interval ◽  
Inclusion Criteria ◽  
Raising Awareness ◽  
Number Of Patients

Levothyroxine suppression therapy (LST) can cause some unfavorable effects on the cardiovascular system in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate ventricular arrhythmia predictors based on electrocardiography (ECG) in patients with DTC with LST. The ECG parameters including QT, corrected QT (QTc), Tp-e intervals, Tp-e/QT, and Tp-e/QTC ratios of 265 patients with DTC who met the inclusion criteria were compared with 100 controls. No difference was observed in the number of patients with DTC and controls with prolonged and borderline QTc interval ( P = .273). Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios were significantly higher in patients ( P = .002, P = .02, P = .003; respectively). Linear regression analysis suggested that male gender was a predictor of higher Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios (β = 4.322, R 2 = 0.024, P = .042; β = 0.016, R 2 = 0.048, P = .005; β = 0.015, R 2 = 0.044, P = .006, respectively). A higher serum fT4 level was found to be associated with a higher Tp-e/QT ratio (β = 0.018, R 2 = 0.089, P = .007). Ventricular arrhythmia indicators were found to be higher in patients with DTC with LST. Defining ventricular arrhythmia predictors through ECG, an easily accessible cardiac diagnostic tool, can be potentially useful in raising awareness of the possible cardiac harm of LST.

scholarly journals Bayesian adaptive design of early-phase clinical trials for precision medicine based on cancer biomarkers

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shinjo Yada
Keyword(s):  
Neural Network ◽  
Clinical Trials ◽  
Precision Medicine ◽  
Early Phase ◽  
Patient Specific ◽  
Specific Gene ◽  
Cancer Type ◽  
Background Characteristics ◽  
Number Of Patients ◽  
Early Phase Clinical Trials

Abstract Cancer tissue samples obtained via biopsy or surgery were examined for specific gene mutations by genetic testing to inform treatment. Precision medicine, which considers not only the cancer type and location, but also the genetic information, environment, and lifestyle of each patient, can be applied for disease prevention and treatment in individual patients. The number of patient-specific characteristics, including biomarkers, has been increasing with time; these characteristics are highly correlated with outcomes. The number of patients at the beginning of early-phase clinical trials is often limited. Moreover, it is challenging to estimate parameters of models that include baseline characteristics as covariates such as biomarkers. To overcome these issues and promote personalized medicine, we propose a dose-finding method that considers patient background characteristics, including biomarkers, using a model for phase I/II oncology trials. We built a Bayesian neural network with input variables of dose, biomarkers, and interactions between dose and biomarkers and output variables of efficacy outcomes for each patient. We trained the neural network to select the optimal dose based on all background characteristics of a patient. Simulation analysis showed that the probability of selecting the desirable dose was higher using the proposed method than that using the naïve method.

scholarly journals Favipiravir antiviral efficacy against SARS-CoV-2 in a hamster model

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jean-Sélim Driouich ◽  
Maxime Cochin ◽  
Guillaume Lingas ◽  
Grégory Moureau ◽  
Franck Touret ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Drug Exposure ◽  
Clinical Evidence ◽  
Antiviral Effect ◽  
Dose Effect ◽  
Plasma Drug ◽  
Hamster Model ◽  
Viral Genomes ◽  
Antiviral Efficacy ◽  
Repurposed Drugs

AbstractDespite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiated before or simultaneously to infection, favipiravir has a strong dose effect, leading to reduction of infectious titers in lungs and clinical alleviation of the disease. Antiviral effect of favipiravir correlates with incorporation of a large number of mutations into viral genomes and decrease of viral infectivity. Antiviral efficacy is achieved with plasma drug exposure comparable with those previously found during human clinical trials. Notably, the highest dose of favipiravir tested is associated with signs of toxicity in animals. Thereby, pharmacokinetic and tolerance studies are required to determine whether similar effects can be safely achieved in humans.

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