Mechanisms of action and adverse effects of the major therapeutic agents in trial for COVID-19 therapeutics: Review of literature

The race to find an effective cure for COVID-19 is on. Most of the candidate drugs in various clinical trials are being re-purposed but none has been approved as at date. It is pertinent for the bedside physicians to understand the mechanisms of action of these agents and their peculiar adverse effects so they are properly guided on the risk/benefit of the drugs they choose in managing COVID-19 patients. Clinicaltrials.gov, the international clinical trials platform of the WHO, the EU clinical trials register and the Cochrane Central Register of Controlled Trials were searched for registered clinical trials. Studies in therapeutic trials were considered eligible for the work. Frequency table was made for the most common trialled drugs and the mechanisms of actions and adverse effects of the selected drugs were reviewed. Ten studies were selected for review in a descending order of their frequency in different therapeutic trials and these are ritonavir, lopinavir, chloroquine/ hydroxychloroquine, interferon, remdesvir, favipravir, umifenovir, darunavir, tocilizumab and methylprednisolone. The bedside physicians need to understand the mechanisms of action of these agents and their peculiar adverse effects for proper guidance on the risk/benefit of the drugs they choose in managing COVID- 19 patients.

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Mechanisms of action and adverse effects of the major therapeutic agents in trial for COVID-19 therapeutics: review of literature

10.22541/au.159415278.83599086 ◽

2020 ◽

Author(s):

Emeka Ogiji ◽

Obumneme Ezeanosike ◽

Casimir Ofor ◽

Edak Ezeanosike ◽

Charles Maduba ◽

...

Keyword(s):

Adverse Effects ◽

Therapeutic Agents ◽

Mechanisms Of Action ◽

Review Of Literature

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Mechanisms of action and adverse effects of the major therapeutic agents in trial for COVID-19 therapeutics: a review of literature.

10.22541/au.159363391.13649260 ◽

2020 ◽

Author(s):

Emeka Ogiji ◽

Obumneme Ezeanosike ◽

Casimir Ofor ◽

Edak Ezeanosike ◽

Charles Maduba ◽

...

Keyword(s):

Adverse Effects ◽

Therapeutic Agents ◽

Mechanisms Of Action ◽

Review Of Literature

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EFFICACY OF SPIRULINA FOR ALLERGIC RHINITIS

10.1101/2021.10.21.21265199 ◽

2021 ◽

Author(s):

Iury Gomes Batista ◽

Osmar Cleyton Person ◽

Fernando Veiga Angelico Junior ◽

Priscila Bogar

Keyword(s):

Clinical Trials ◽

Allergic Rhinitis ◽

Randomized Clinical Trials ◽

Nasal Congestion ◽

Control Group ◽

Cochrane Central Register ◽

Level Of Evidence ◽

Runny Nose ◽

Trial Quality ◽

Central Register

Introduction: Allergic rhinitis is a condition of high prevalence in the population and widely studied, with several treatments being consecrated for its control. Spirulina is a dietary supplement that modulates immune function, and has been shown to modulate the inflammatory response of allergic rhinitis. Purpose: To evaluate spirulina in the treatment and control of allergic rhinitis. Material and Methods: This is a systematic review of randomized clinical trials. Searches were performed for randomized clinical trials relating spirulina to allergic rhinitis in five electronic databases: Cochrane - Central Register of Controlled Trials - CENTRAL (2021), PUBMED (1966-2021), EMBASE (1974-2021), LILACS (1982-2021) AND SCOPUS (2021). Two investigators independently extracted data and assessed trial quality. Results: Two clinical trials involving a total of 215 patients were included. Both studies assessed the efficacy of spirulina in improving allergic rhinitis as the primary outcome. The first study described a significant reduction in runny nose, nasal congestion and itching over time of medication use (p 0.001) and in the second study the prevalence of rhinorrhea (P = 0.021), nasal congestion or obstruction (P = 0.039) and decreased smell (P = 0.030) were significantly less in the experimental group than in the control group. Conclusions: The included studies were in favor of the use of spirrulina. However, the level of evidence is very low and limited. We should have caution due to the small number of clinical trials and participants in these studies. It is recommended to carry out new RCTs following the CONSORT standardization.

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Systematic Review of Randomized Clinical Trials of Acupressure Therapy for Primary Dysmenorrhea

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/169692 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Hui-ru Jiang ◽

Shuang Ni ◽

Jin-long Li ◽

Miao-miao Liu ◽

Ji Li ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Statistical Analysis ◽

Adverse Events ◽

Randomized Clinical Trials ◽

Controlled Trials ◽

Cochrane Central Register ◽

Primary Dysmenorrhea ◽

Randomized Controlled ◽

Central Register

The evidence of acupressure is limited in the management of dysmenorrhea. To evaluate the efficacy of acupressure in the treatment of primary dysmenorrhea based on randomized controlled trials (RCTs), we searched MEDLINE, the Chinese Biomedical Database (CBM), and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception until March 2012. Two reviewers independently selected articles and extracted data. Statistical analysis was performed with RevMan 5.1 software. Eight RCTs were identified from the retrieved 224 relevant records. Acupressure improved pain measured with VAS (−1.41 cm 95% CI [−1.61, −1.21]), SF-MPQ at the 3-month followup (WMD −2.33, 95% CI [−4.11, −0.54]) and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]), and MDQ at the 3-month followup (WMD −2.31, 95% CI [−3.74, −0.87]) and 6-month followup (WMD −4.67, 95% CI [−7.30, −2.04]). All trials did not report adverse events. These results were limited by the methodological flaws of trials.

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Acupuncture in oncological pain relief: A systematic review of randomized clinical trials

Fisioterapia em Movimento ◽

10.1590/fm.2021.34203 ◽

2021 ◽

Vol 34 ◽

Author(s):

Michel Marcos Dalmedico ◽

Caroline Machado de Toledo ◽

Paula Karina Hembecker ◽

Juliana Londero Silva Ávila ◽

Chayane Karla Lucena de Carvalho ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Cancer Pain ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Cochrane Central Register ◽

Opioid Use ◽

Central Register ◽

Considerable Impact ◽

Analgesic Use

Abstract Introduction: Cancer pain has a considerable impact on patients’ health and quality of life, and its treatment is essentially based on opioid use. Objective: To report the effectiveness of acupuncture in relieving cancer pain (secondary to the disease or to the corresponding therapy) or in decreasing opioid use compared to other interventions. Methods: A systematic review of randomized clinical trials was conducted following the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. The trials were selected from the PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Results: The search strategy resulted in the inclusion of eight trials, of which five compared acupuncture and drug therapy and three compared acupuncture and placebo. Seven trials reported decreased pain and analgesic use. The trials showed clinical heterogeneity, making a meta-analysis unfeasible. Conclusion: The findings herein provided no robust evidence to support the routine use of acupuncture as an adjuvant therapy in the treatment of cancer pain. However, its use is promising since the results showed a trend toward decreased pain and analgesic use, thus justifying further studies in the future.

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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 ◽

10.3390/life11090927 ◽

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.

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Effect of Rapid Maxillary Expansion on Mandibular Rotation—A Systematic Review

The Journal of Indian Orthodontic Society ◽

10.1177/0301574219897318 ◽

2020 ◽

Vol 54 (1) ◽

pp. 5-13

Author(s):

Priyanka Chhutani ◽

Sonali Deshmukh ◽

Sandeep Jethe ◽

Sanket Agarkar ◽

Sujata Yerawadekar ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Rapid Maxillary Expansion ◽

Controlled Trials ◽

Cochrane Central Register ◽

Maxillary Expansion ◽

Eligibility Criteria ◽

Maxillary Molars ◽

Central Register ◽

Clinical Trials Registry

Objective: To evaluate the effect of rapid maxillary expansion (RME) on mandibular rotation. Materials and Method: A systematic review of articles selected from 4 electronic databases—PUBMED, Cochrane Central Register of Controlled Trials, Clinical Trials Registry, and Google Scholar—was carried out. Additional studies were hand-searched and retrieved from the reference lists of relevant articles. Studies published till August, 2019, were included in this study. Results: A total of 28 articles were identified through electronic database searching. 16 articles were obtained after elimination of duplicates which were then screened. Full-text articles were assessed according to the eligibility criteria. 2 randomized controlled trials (RCTs) and 14 clinical trials (CTs) were identified for inclusion in the review. These studies effectively highlighted the effect of RME on mandibular rotation, primarily in the clockwise direction. Conclusion: There is a moderate sum of evidence to illustrate the effect of RME on mandibular rotation. It can be concluded that RME brings about clockwise rotation of the mandible, ie in downward and backward directions, thereby increasing the lower anterior facial height. This effect could be attributed to the vertical maxillary movement and the extrusion of the maxillary molars.

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Meta-analysis of drug efficacy in adult vs pediatric trials of patients with PGTC seizures

Neurology ◽

10.1212/wnl.0000000000009325 ◽

2020 ◽

Vol 94 (17) ◽

pp. e1845-e1852

Author(s):

Douglas R. Nordli ◽

Emilia Bagiella ◽

Alexis Arzimanoglou ◽

Jinping Wang ◽

Dinesh Kumar ◽

...

Keyword(s):

Clinical Trials ◽

Seizure Frequency ◽

Pediatric Population ◽

Meta Analysis ◽

Evaluation Criteria ◽

Drug Efficacy ◽

Cochrane Central Register ◽

Central Register ◽

Adults And Children ◽

Clonic Seizures

ObjectiveA meta-analysis of published studies was performed to determine whether the efficacy of antiseizure drugs in adults with primary generalized tonic-clonic seizures (PGTCS) is comparable with that in the pediatric population (2–12 years of age).MethodsElectronic searches were conducted in EMBASE, Medline, and the Cochrane Central Register of Controlled Trials for clinical trials of PGTCS in adults and children 2–12 years of age. Neurologists used standardized search and study evaluations to select eligible trials. Median percent reduction in seizure frequency from baseline and ≥50% responder rates were used to compare drug efficacy in adults and children.ResultsAmong 7 adjunctive-therapy PGTCS trials in adults and children (2–12 years of age) that met evaluation criteria, effect sizes were consistent between adults and children for lamotrigine and topiramate. The baseline-subtracted median percent seizure reduction in seizure frequency ranged from 50.0% to 79.7% in children and 57.0% to 64.0% in adults. The ≥50% responder rate was similar between children and adults in a topiramate study (50% in children compared with 58% in adults).ConclusionsThis meta-analysis supports the use of drug response from antiseizure drug clinical trials for PGTCS in adults to predict comparable treatment response in children 2–12 years of age with PGTCS.

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Efficacy of Adjunctive Treatments Added to Olanzapine or Clozapine for Weight Control in Patients with Schizophrenia: A Systematic Review and Meta-Analysis

The Scientific World JOURNAL ◽

10.1155/2015/970730 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Yun-Jung Choi

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Effects ◽

Weight Reduction ◽

Weight Control ◽

Randomized Clinical Trials ◽

Psychiatric Symptoms ◽

Meta Analysis ◽

Cochrane Central Register ◽

Meta Analyses

Objectives. This study was conducted to review systematically adjunctive treatments for weight reduction in patients with schizophrenia and compare efficacies of clinical trials through meta-analysis, so as to provide effective clinical guideline regarding weight control for patients taking atypical antipsychotics.Methods. Candidate clinical trials were identified through searching the Cochrane Central Register of Controlled Trials, PubMed, and PsycINFO. Fourteen randomized clinical trials were included for systematic review and meta-analysis from 132 potential trials. The Comprehensive Meta-Analysis version 2 was used for meta-analysis.Results. Difference in means and significances from meta-analyses regarding weight control by adjunctive treatments showed that topiramate, aripiprazole, or sibutramine was more effective than metformin or reboxetine. Psychiatric evaluations did not show statistically significant changes between treatment groups and placebo groups except topiramate adjunctive treatments. Adverse effects regarding adjunctive therapies were tolerable and showed statistically no significances compared to control groups.Conclusion. Though having several reports related to exacerbation of psychiatric symptoms, topiramate and aripiprazole are more efficacious than other medications in regard to weight reduction and less burden of critical adverse effects as well as being beneficial for clinical improvement.

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Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.562315 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shixue Chen ◽

Zhibo Zhang ◽

Xuan Zheng ◽

Haitao Tao ◽

Sujie Zhang ◽

...

Keyword(s):

Clinical Trials ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Subsequent Treatment ◽

Drug Combinations ◽

Cochrane Central Register ◽

First Line ◽

Response Efficacy ◽

Central Register ◽

Cancer Types

BackgroundImmune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have demonstrated promise in treating a variety of advanced cancers; however, little is known regarding their efficacy under various clinical situations, including different cancer types, treatment lines, drug combinations, and therapeutic regimens.MethodsPublished articles and conference abstracts (in English) in PubMed, Embase, the Cochrane Central Register, and Web of Science were searched up to February 10, 2020. The data were analyzed by the meta-analysis program in Stata.ResultsA total of 16,400 patients from 91 clinical trials were included in this meta-analysis. PD-1/PD-L1 inhibitors had a mean ORR of 19.56% (95% CI: 15.09–24.03), a median TTR of 2.05 months (m) (95%CI: 1.85–2.26), and a median DOR of 10.65 m (95%CI: 7.78–13.52). First-line treatment had a higher ORR (36.57% vs. 13.18%) but a shorter DOR (9.00 m vs. 13.42 m) compared to the second-line or subsequent treatment. Immunotherapy combined with chemotherapy (I+C) (46.81% [95%CI: 36.02–57.60]) had a statistically significant higher ORR compared to immunotherapy (I) (17.75% [95%CI: 14.47–21.03]) or immunotherapy combined with immunotherapy (I+O) (12.25% [95%CI: 1.56–22.94]), while I+C (8.09 m [95%CI: 6.86–9.32]) appeared to reduce the DOR compared to I (12.39 m [95%CI: 7.60–17.18]). PD-1 inhibitors were associated with better ORR (21.65% vs. 17.60%) and DOR (11.26 m vs. 10.03 m) compared to PD-L1 inhibitors. There were no significant differences in TTR under different situations.ConclusionsPD-1/PD-L1 inhibitors were promising immunotherapeutic agents to achieve satisfactory response efficacies with different cancer types, treatment lines, drug combinations, and therapeutic regimens. This comprehensive summary of the response efficacy of PD-1/PD-L1 inhibitors serves as a reference for clinicians to make evidence-based decisions.

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