Risk versus Benefit of Using Hydroxychloroquine to Treat Patients with COVID-19

Hydroxychloroquine (HCQ), also known by its trade name Plaquenil®, has been used for over 50 years as a treatment for malaria, systemic lupus erythematosus, and rheumatoid arthritis. As the COVID-19 pandemic emerged in the United States and globally in early 2020, HCQ began to garner attention as a potential treatment and as prophylaxis against COVID-19. Preliminary data indicated that HCQ as well as chloroquine (CQ) possessed in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early clinical data from China and France reported that HCQ and CQ were associated with viral load reduction and clinical improvement in patients with COVID-19 compared to control groups; however, an overwhelming number of randomized controlled trials, meta-analyses, and systematic reviews have since concluded that HCQ used alone, or in combination with azithromycin (AZ), provides no mortality or time-to-recovery benefit in hospitalized patients with COVID-19. Additionally, these same trials reported adverse events including cardiac, neuropsychiatric, hematologic, and hepatobiliary manifestations in patients with COVID-19 whom had been treated with HCQ. This review article summarizes the available data pertaining to the adverse events associated with HCQ use, alone or in combination with azithromycin, in patients with COVID-19 in order to fully assess the risk versus benefit of treating COVID-19 patients with these agents. The results of this review lead us to conclude that the risks of adverse events associated with HCQ use (with or without AZ) outweigh the potential clinical benefits and thus recommend against its use in the treatment or prevention of COVID-19.

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Adverse Effects of Natural Products: A Brief Pre-Systematic Review

Current Nutraceuticals ◽

10.2174/2665978601999200702163914 ◽

2020 ◽

Vol 01 ◽

Author(s):

Carla Pires ◽

Ana Fernandes

Keyword(s):

Systematic Review ◽

Adverse Event ◽

Natural Products ◽

Adverse Events ◽

In Vitro Study ◽

Google Scholar ◽

Inclusion Criteria ◽

Exclusion Criteria ◽

Meta Analyses

Background: Natural products are commonly used for treating health problems. These products may be associated with adverse events, which are defined as "noxious and unintended response to a medicinal product" by the European Medicine Agency. Objectives: To identify studies describing at least one adverse event (or with potential to promote an adverse event) related to the use of natural products, as well as to describe the involved product(s) and adverse event(s). Methods: A pre-systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Keywords: "natural product(s)" and ["adverse drug reaction(s)" or "adverse effect(s)"]. Screened databases: PubMed, SciELO, DOAJ and Google Scholar. Inclusion criteria: papers describing at least one adverse event associated with the use of natural products and published between 2017 and 2019. Exclusion criteria: Repeated studies, reviews and papers written in other languages than English, Portuguese, French or Spanish. Results: 104 studies were identified (20 PubMed; 0 SciELO; 2 DOAJ; 82 Google Scholar), but only 10 were selected (4 PubMed and 6 Google Scholar): 1 in-vitro study; 2 non-clinical studies, 1 study reporting in-vitro and clinical data and 5 studies were cases reports. Globally, 997 reports of adverse drug reactions with natural products were identified, mainly non-severe cases. Conclusion: Since a limited number of studies was found, we conclude that adverse events due to natural products may be underreported, or natural products may have a good safety profile. This review contributes for assuring the safety of natural products consumers, by evaluating the knowledge/information on the potential adverse events and interactions of these products.

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Kratom from Head to Toe—Case Reviews of Adverse Events and Toxicities

Current Emergency and Hospital Medicine Reports ◽

10.1007/s40138-019-00194-1 ◽

2019 ◽

Vol 7 (4) ◽

pp. 141-168 ◽

Cited By ~ 5

Author(s):

Emad Alsarraf ◽

Jamie Myers ◽

Sarah Culbreth ◽

John Fanikos

Keyword(s):

Adverse Events ◽

Case Reports ◽

In Vivo Studies ◽

Poison Control ◽

Cross Sectional ◽

Randomized Controlled ◽

Reversible Encephalopathy ◽

Neonatal Withdrawal

Abstract Purpose of Review This review describes case reports for patients with kratom-associated adverse events in order to assist clinicians with patient management. A stepwise approach is proposed for assessing active kratom users as well as considerations for the management of toxicities or withdrawal. Recent Findings Multiple in vitro and in vivo studies illustrate the pharmacologic and toxicologic effects of kratom extract. No randomized controlled trials in humans exist that assess the safety and efficacy of the substance. Cross-sectional surveys from active users and reports from poison control centers have shown acute and chronic physiological and psychological adverse events. Summary Reports of adverse effects associated with kratom use have demonstrated hypothyroidism, hypogonadism, hepatitis, acute respiratory distress syndrome, posterior reversible encephalopathy syndrome, seizure, and coma. Overdose toxidrome leads to respiratory failure, cardiac arrest, and fatalities. Adult and neonatal withdrawal symptoms have also occurred. Clinicians should be aware of the risks and benefits of kratom use.

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Belimumab restores Treg/Th17 balance in patients with refractory systemic lupus erythematosus

Lupus ◽

10.1177/0961203318797425 ◽

2018 ◽

Vol 27 (12) ◽

pp. 1926-1935 ◽

Cited By ~ 5

Author(s):

M Prete ◽

P Leone ◽

M A Frassanito ◽

V Desantis ◽

C Marasco ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

Lupus Erythematosus ◽

Standard Therapy ◽

B Lymphocyte ◽

Specific Inhibitor ◽

The United States ◽

Systemic Lupus ◽

The Mean

Belimumab, a specific inhibitor of the soluble B lymphocyte stimulator (BlyS), is the first biological drug approved by the United States Food and Drug Administration for the treatment of patients with active systemic lupus erythematosus (SLE) refractory to standard therapy. Given that an imbalance between regulatory T cells (Treg) and interleukin (IL)-17A-secreting T cells (Th17) has been reported in various autoimmune disorders, we assessed the frequency of both Treg and Th17 peripheral blood populations before and after belimumab administration in 20 patients with active SLE refractory to standard therapy. After six months of treatment, the mean SELENA-SLEDAI score as well as the mean anti-double-stranded DNA antibody titers were significantly decreased. In addition, we observed a significant increase in Treg percentages and a parallel, significant decrease in Th17 percentages, accompanied by significantly reduced serum levels of IL-21. In vitro studies showed that Treg purified from belimumab-treated patients were fully functional and displayed a suppressor function similar to that of Treg purified from healthy donors. Belimumab can restore Treg/Th17 balance in SLE patients with uncontrolled disease activity, and this results in decreased flare rate and reduced glucocorticoid dosage.

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A systematic review and meta-analysis of randomized controlled trials for the reduction of surgical site infection in closed incision management versus standard of care dressings over closed vascular groin incisions

Vascular ◽

10.1177/1708538119890960 ◽

2020 ◽

Vol 28 (3) ◽

pp. 274-284 ◽

Cited By ~ 3

Author(s):

Alexander Gombert ◽

Ellen Dillavou ◽

Ralph D’Agostino ◽

Leah Griffin ◽

Julie M Robertson ◽

...

Keyword(s):

Vascular Surgery ◽

Surgical Site Infection ◽

Meta Analysis ◽

Site Infection ◽

Infection Rates ◽

Control Groups ◽

Randomized Controlled ◽

Risk Patients ◽

Meta Analyses ◽

And Control

Objective Surgical site infection after groin incision is a common complication and a financial burden to patients and healthcare systems. Closed incision negative pressure therapy (ciNPT) has been associated with decreased surgical site infection rates in published literature. This meta-analysis examines the effect of ciNPT (PREVENA™ Incision Management System; KCI, San Antonio, TX) versus traditional postsurgical dressing use in reducing surgical site infection rates over closed groin incisions following vascular surgery. Methods A systematic literature search using PubMed, OVID, EMBASE, and QUOSA was performed on 3 January 2019, by two independent researchers and focused on publications between 1 January 2005 and 31 December 2018. The review conformed to the statement and reporting check list of the Preferred Reporting Items for Systematic Reviews and Meta Analyses. Inclusion criteria included abstract or manuscript written in English, published studies, conference abstracts, randomized controlled trials (RCTs), ciNPT usage over closed groin incisions in vascular surgery, comparison of ciNPT use and traditional dressings, study endpoint/outcome of surgical site infection, and study population of >10. Characteristics of study participants, surgical procedure, type of dressing used, duration of treatment, incidence of surgical site infection, and length of follow-up were extracted. Weighted odds ratios and 95% confidence intervals were calculated to pool study and control groups in each publication for analysis. Treatment effects were combined using Mantel-Haenszel risk ratios, and the Chi-Square test was used to assess heterogeneity. Overall, high-risk patients, normal-risk patients, and Szilagyi I, II, III outcomes were assessed between ciNPT and control groups. The Cochrane Collaboration tool was utilized to assess the risk of bias for all studies included in the analysis. Results A total of 615 articles were identified from the literature search. After removal of excluded studies and duplicates, six RCT studies were available for analysis. In these studies, a total of 362 patients received ciNPT, and 371 patients received traditional dressings (control). Surgical site infection events occurred in 41 ciNPT patients and 107 control patients. The heterogeneity test was nonsignificant ( p > 0.05). The overall RCT meta-analysis showed a highly significant effect in favor of ciNPT (OR = 3.06, 95% CI [2.05, 4.58], p < 0.05). High-risk, normal-risk, Szilagyi I, and Szilagyi II meta-analyses were also statistically significant in favor of ciNPT use ( p < 0.05). The varying RCT inclusion/exclusion criteria, such as differences in procedure types, and patient populations form the major limitations of this study. Conclusions A statistically significant reduction in the incidence of surgical site infection was seen following ciNPT usage in patients undergoing vascular surgery with groin incisions.

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Dexmedetomidine Versus Propofol Sedation in Flexible Bronchoscopy: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis

10.21203/rs.3.rs-1218948/v1 ◽

2022 ◽

Author(s):

Barak Pertzov ◽

Boris Krasulya ◽

Karam Azem ◽

Yael Shostak ◽

Shimon Izhakian ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Controlled Trial ◽

Meta Analysis ◽

Flexible Bronchoscopy ◽

Control Groups ◽

Randomized Controlled ◽

Study Results ◽

Alpha2 Adrenoceptor ◽

And Control

Abstract Background:Dexmedetomidine (DEX), is a highly selective alpha2 adrenoceptor (α2-AR) agonist, successfully used in various procedures including flexible bronchoscopy. Randomized controlled trials (RCTs) evaluating DEX sedation during bronchoscopy report equivocal results regarding respiratory and hemodynamic outcomes. Methods We conducted an RCT to evaluate the efficacy of dexmedetomidine compared to propofol for sedation during bronchoscopy. The primary outcome was desaturation events, secondary outcomes were transcutaneous Pco2 level, hemodynamic adverse events and physician and patient satisfaction. We have also conducted A systematic review and meta-analysis of all RCTs evaluating DEX sedation during flexible bronchoscopy, included current study results.ResultsOverall, 63 patients were included, 30 and 33 in the DEX and propofol groups, respectively. The number of desaturation events was similar between groups, median (IQR) 1 (0-1) and 1 (0-2) in the DEX and control groups, respectively (P=0.29). Median desaturation time was 1 (0-2) and 1 (0-3) minutes in the DEX and control groups, respectively (P=0.48). Adverse events included hypotension, 33% vs 21.1% in intervention and control groups, respectively (P=0.04), bradycardia, cough, and delayed recovery from sedation. Total adverse events were 22 and 7 in DEX and propofol groups, respectively (P=0.009). The pooled meta-analysis included 13 trials (1604 participants) showed a significantly lower rate of desaturation events in the DEX group (RR 0.67, 95% CI 0.57 to 0.79) with a significantly higher rate of hypotension and bradycardia events (RR 1.55, 95% CI 1.16 to 2.06 and RR 1.91, 95% CI 1.04 to 3.5, respectively)ConclusionDexmedetomidine sedation resulted in a significantly reduced rate of desaturation events in comparison to propofol, midazolam and fentanyl. However, it was also associated with a higher rate of hypotension and bradycardia.Trial registration : NCT04211298, registration date: 26/12/2019

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The Efficacy of Cognitive Behavioral Therapy for Adults With ADHD: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Journal of Attention Disorders ◽

10.1177/1087054716664413 ◽

2016 ◽

Vol 24 (6) ◽

pp. 875-888 ◽

Cited By ~ 16

Author(s):

Zoe Young ◽

Nima Moghaddam ◽

Anna Tickle

Keyword(s):

Systematic Review ◽

Cognitive Behavioral Therapy ◽

Active Control ◽

Effect Size ◽

Behavioral Therapy ◽

Controlled Trials ◽

Control Groups ◽

Total N ◽

Randomized Controlled ◽

Meta Analyses

Objective: To systematically review the literature on published randomized controlled trials (RCTs) of cognitive behavioral therapy (CBT) for adult ADHD and to establish the effectiveness of CBT in reducing ADHD symptoms. Method: A systematic review of nine RCTs and two subsequent meta-analyses of eight of the studies were conducted. Results: Just nine studies were identified, of generally good quality but with some limitations. Four trials (total N = 160) compared CBT with waiting list controls, and three trials (total N = 191) compared CBT with appropriate active control groups. Meta-analyses showed that CBT was superior to waiting list with a moderate to large effect size (standardized mean difference [SMD] = 0.76, 95% confidence interval [CI] [0.21, 1.31], p = .006) and superior to active control groups with a small to moderate effect size (SMD = 0.43, 95% CI [0.14, 0.71], p = .004). Conclusion: These results give support to the efficacy of CBT in reducing symptoms of ADHD post-intervention.

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Efficacy, Safety, and Tolerability of Gepotidacin (GSK2140944) in the Treatment of Patients with Suspected or Confirmed Gram-Positive Acute Bacterial Skin and Skin Structure Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02095-16 ◽

2017 ◽

Vol 61 (6) ◽

Cited By ~ 21

Author(s):

William O'Riordan ◽

Courtney Tiffany ◽

Nicole Scangarella-Oman ◽

Caroline Perry ◽

Mohammad Hossain ◽

...

Keyword(s):

Adverse Events ◽

Clinical Utility ◽

The United States ◽

Phase 2 ◽

Efficacy And Safety ◽

Open Label ◽

Gram Positive ◽

Double Blind ◽

Skin Structure

ABSTRACT Gepotidacin is a novel, first-in-class, triazaacenaphthylene antibacterial agent which has in vitro activity against causative pathogens of acute bacterial skin and skin structure infections (ABSSSIs). This phase 2, randomized, 2-part, multicenter, dose-ranging, response-adaptive study with optional intravenous-oral switch evaluated the efficacy and safety of gepotidacin for the treatment of Gram-positive ABSSSIs in 122 adult patients in the United States. The study had a double-blind phase (part 1; intravenous [750 mg or 1,000 mg every 12 h {q12h}]) and an open-label phase (part 2; intravenous [750 mg q12h, 1,000 mg q12h, or 1,000 q8h]). The primary endpoint was a composite of efficacy and safety which consisted of the early cure rate and the withdrawal rate due to drug-related adverse events and utilized a clinical utility index for dose selection. At the early efficacy visit (48 to 72 h after the first dose), the 750-mg q12h and 1,000-mg q8h groups met prespecified success criteria for clinical utility in terms of efficacy and safety; however, the 1,000-mg q12h group did not meet these criteria due to observed lower efficacy rates. The most frequently reported adverse events were nausea (20%) and diarrhea (13%). These encouraging phase 2 results demonstrate the potential for gepotidacin to meet the medical need for novel antibacterial agents to treat ABSSSIs due to drug-resistant pathogens through a unique mechanism of action. (This study has been registered at ClinicalTrials.gov under registration no. NCT02045797.)

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Lidocaine vs. Other Local Anesthetics in the Development of Transient Neurologic Symptoms (TNS) Following Spinal Anesthesia: A Meta-Analysis of Randomized Controlled Trials

Journal of Clinical Medicine ◽

10.3390/jcm9020493 ◽

2020 ◽

Vol 9 (2) ◽

pp. 493 ◽

Cited By ~ 1

Author(s):

Chang-Hoon Koo ◽

Hyun-Jung Shin ◽

Sung-Hee Han ◽

Jung-Hee Ryu

Keyword(s):

Randomized Controlled Trials ◽

Spinal Anesthesia ◽

Local Anesthetics ◽

Meta Analysis ◽

Control Group ◽

Controlled Trials ◽

Control Groups ◽

Lidocaine Group ◽

Randomized Controlled ◽

Meta Analyses

The use of lidocaine in spinal anesthesia may increase the risk of transient neurological symptoms (TNS) according to previous meta-analyses. However, the previous meta-analyses lacked data on some other local anesthetics and thus, more evaluations are still needed to compare the effect of lidocaine on the development of TNS. The objective of this study was to compare the risk of TNS according to lidocaine versus other local anesthetics in patients undergoing spinal anesthesia. A total of 39 randomized controlled trials with 4733 patients were analyzed. The incidence of TNS was 10.8% in the lidocaine group and was 2.2% in the control groups (risk ratio (RR) 4.12, 95% confidence interval (CI) 3.13 to 5.43, p < 0.001). In subgroup analysis, lidocaine increased the incidence of TNS compared with other local anesthetics except mepivacaine, ropivacaine or sameridine. The risk of TNS was higher in the hyperbaric (p < 0.001) or isobaric lidocaine (p < 0.001) group compared with the control group, but there were no differences found between the two groups when hypobaric lidocaine was administered (p = 1.00). This study confirmed that lidocaine for spinal anesthesia still causes TNS more frequently than most other local anesthetics, especially when hyperbaric or isobaric lidocaine was used.

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Protocol violations in López-Medina et al.: 38 switched ivermectin (IVM) and placebo doses, failure of blinding, widespread IVM sales OTC in Cali, and nearly identical AEs for the IVM and control groups

10.31219/osf.io/u7ewz ◽

2021 ◽

Author(s):

David Scheim ◽

Jennifer A. Hibberd ◽

Juan Chamie-Quintero

Keyword(s):

Randomized Controlled Trial ◽

Adverse Events ◽

Controlled Trial ◽

Control Group ◽

High Dose ◽

Control Groups ◽

Over The Counter ◽

Randomized Controlled ◽

Widespread Availability ◽

And Control

A randomized controlled trial for treatment of mild cases of COVID-19 conducted in Cali, Colombia reported no statistically significant differences in outcomes for its ivermectin (IVM) and placebo arms. A striking anomaly, however, was that certain adverse events (AEs) that are distinctive for the study’s high-dose IVM use occurred at nearly identical rates in its IVM and placebo arms. The backdrop for these indicators of IVM use in study controls was widespread sales of IVM for COVID-19 in the Cali area during the study period, with 1.6 IVM doses sold over the counter for each case of COVID-19. The study compounded these risks of contamination of the control arm with critical errors in blinding and segregation of IVM v. placebo doses. A labeling error substituted IVM for placebo doses of 38 patients. Also, 5% dextrose solution was used for several weeks as a placebo, easily distinguishable from bitter tasting IVM. Given widespread availability and sales of IVM in Cali, lapses in segregation and blinding of IVM and control doses, and IVM-characteristic AEs in controls, the integrity of the study’s control arm was violated. Some useful information can nevertheless be salvaged from outcomes of this study’s IVM treatment arm, which had 0 deaths and generally mild symptoms, with AEs typical for high-dose IVM (replicated in the control group) that were generally mild and transient.

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The Use of Androgen Priming in Women with Reduced Ovarian Reserve Undergoing Assisted Reproductive Technology

Seminars in Reproductive Medicine ◽

10.1055/s-0041-1735646 ◽

2021 ◽

Author(s):

Alison Richardson ◽

Kanna Jayaprakasan

Keyword(s):

Ovarian Reserve ◽

Ovarian Response ◽

Reproductive Technology ◽

Ivf Outcome ◽

Poor Ovarian Response ◽

Vitro Fertilization ◽

Randomized Controlled ◽

Meta Analyses

AbstractAndrogen priming with either dehydroepiandrosterone (DHEA) or testosterone has been suggested as an adjunct to improve in vitro fertilization (IVF) outcomes in women with diminished ovarian reserve (DOR). Numerous studies have investigated the effects of both DHEA and testosterone on IVF outcome. The results were inconsistent, and the quality of most studies is substandard. Meta-analyses have consistently reported that DHEA does appear to significantly improve IVF outcome in women with predicted or proven poor ovarian response (POR), but these have included some normal responders and/or nonrandomized studies. Our meta-analyses including randomized controlled trials (RCTs) incorporating only women with DOR or POR suggest that DHEA confers no benefit. While meta-analyses of RCTs on the use of testosterone in women with DOR or POR showed an improved IVF outcome, most studies included are of low quality with high risk of bias. When analysis of data from studies of only low-risk bias was performed, such a benefit with testosterone was not observed. Although recruitment may well be a challenge, a large, well-designed RCT is, however, still warranted to investigate whether or not androgen priming with either DHEA or testosterone should be recommended as an adjuvant treatment for women with DOR or POR undergoing IVF.

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