The effect of analgesics on stimulus evoked pain-like behaviour in animal models for chemotherapy induced peripheral neuropathy- a meta-analysis

AbstractChemotherapy induced painful peripheral neuropathy (CIPN) is a common dose-limiting side effect of several chemotherapeutic agents. Despite large amounts of human and animal studies, there is no sufficiently effective pharmacological treatment for CIPN. Although reducing pain is often a focus of CIPN treatment, remarkably few analgesics have been tested for this indication in clinical trials. We conducted a systematic review and meta-analyses regarding the effects of analgesics on stimulus evoked pain-like behaviour during CIPN in animal models. This will form a scientific basis for the development of prospective human clinical trials. A comprehensive search identified forty-six studies. Risk of bias (RoB) analyses revealed that the design and conduct of the included experiments were poorly reported, and therefore RoB was unclear in most studies. Meta-analyses showed that administration of analgesics significantly increases pain threshold for mechanical (SMD: 1.68 [1.41; 1.82]) and cold (SMD: 1. 41 [0.99; 1.83]) evoked pain. Subgroup analyses revealed that dexmedetomidine, celecoxib, fentanyl, morphine, oxycodone and tramadol increased the pain threshold for mechanically evoked pain, and lidocaine and morphine for cold evoked pain. Altogether, this meta-analysis shows that there is ground to investigate the use of morphine in clinical trials. Lidocaine, dexmedetomidine, celecoxib, fentanyl, oxycodone and tramadol might be good alternatives, but more animal-based research is necessary.

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Hydroxychloroquine/Chloroquine in COVID-19 With Focus on Hospitalized Patients - A Systematic Review

10.1101/2022.01.11.22269069 ◽

2022 ◽

Author(s):

Daniel Freilich ◽

Jennifer Victory ◽

Anne Gadomski

Keyword(s):

Clinical Trials ◽

Animal Models ◽

Animal Studies ◽

Randomized Clinical Trials ◽

Hospitalized Patients ◽

Safety Issues ◽

Meta Analyses ◽

In The Beginning ◽

Almost All

Background In the beginning of the COVID-19 pandemic, many hospitalized patients received empiric hydroxychloroquine/chloroquine (HC/CQ). Although some retrospective-observational trials suggested potential benefit, all subsequent randomized clinical trials (RCTs) failed to show benefit and use generally ceased. Herein, we summarize key studies that clinicians advising patients on HC/CQ efficacy:safety calculus in hospitalized COVID-19 patients would want to know about in a practical one-stop-shopping source. Methods Pubmed and Google were searched on November 4, 2021. Search words included: COVID-19, hydroxychloroquine, chloroquine, in vitro, animal studies, clinical trials, and meta-analyses. Studies were assessed for import and included if considered impactful for benefit:risk assessment. Results These searches led to inclusion of 12 in vitro and animal reports; 12 retrospective-observational trials, 19 interventional clinical trials (17 RCTs, 1 single-arm, 1 controlled but unblinded), and 51 meta-analyses in hospitalized patients. Inconsistent efficacy was seen in vitro and in animal studies for coronaviruses and nil in SARS-CoV-2 animal models specifically. Most retrospective-observational studies in hospitalized COVID-19 patients found no efficacy; QT prolongation and increased adverse events and mortality were reported in some. All RCTs and almost all meta-analyses provided robust data showing no benefit in overall populations and subgroups, yet concerning safety issues in many. Conclusions HC/CQ have inconsistent anti-coronavirus efficacy in vitro and in animal models, and no convincing efficacy yet substantial safety issues in the overwhelming majority of retrospective-observational trials, RCTs, and meta-analyses in hospitalized COVID-19 patients. HC/CQ should not be prescribed for hospitalized COVID-19 patients outside of clinical trials.

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Role of Adipokines and Perivascular Adipose Tissue in Abdominal Aortic Aneurysm: A Systematic Review and Meta-Analysis of Animal and Human Observational Studies

Frontiers in Endocrinology ◽

10.3389/fendo.2021.618434 ◽

2021 ◽

Vol 12 ◽

Author(s):

Shivshankar Thanigaimani ◽

Jonathan Golledge

Keyword(s):

Systematic Review ◽

Adipose Tissue ◽

Animal Models ◽

Animal Studies ◽

Meta Analysis ◽

Aortic Aneurysms ◽

Perivascular Adipose Tissue ◽

Abdominal Aortic ◽

Meta Analyses

Improved understanding of abdominal aortic aneurysms (AAA) pathogenesis is required to identify treatment targets. This systematic review summarized evidence from animal studies and clinical research examining the role of adipokines and perivascular adipose tissue (PVAT) in AAA pathogenesis. Meta-analyses suggested that leptin (Standardized mean difference [SMD]: 0.50 [95% confidence interval (CI): −1.62, 2.61]) and adiponectin (SMD: −3.16 [95% CI: −7.59, 1.28]) upregulation did not significantly affect AAA severity within animal models. There were inconsistent findings and limited studies investigating the effect of resistin-like molecule-beta (RELMβ) and PVAT in animal models of AAA. Clinical studies suggested that circulating leptin (SMD: 0.32 [95% CI: 0.19, 0.45]) and resistin (SMD: 0.63 [95% CI 0.50, 0.76]) concentrations and PVAT to abdominal adipose tissue ratio (SMD: 0.56 [95% CI 0.33, 0.79]) were significantly greater in people diagnosed with AAA compared to controls. Serum adiponectin levels were not associated with AAA diagnosis (SMD: −0.62 [95% CI −1.76, 0.52]). One, eight, and one animal studies and two, two, and four human studies had low, moderate, and high risk-of-bias respectively. These findings suggest that AAA is associated with higher circulating concentrations of leptin and resistin and greater amounts of PVAT than controls but whether this plays a role in aneurysm pathogenesis is unclear.

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Extracorporeal shockwave therapy in spinal cord injury, early to advance to clinical trials? A systematic review and meta-analysis on animal studies

The Neuroradiology Journal ◽

10.1177/19714009211026899 ◽

2021 ◽

pp. 197140092110268

Author(s):

Seyedeh Niloufar Rafiei Alavi ◽

Arian Madani Neishaboori ◽

Mahmoud Yousefifard

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Clinical Trials ◽

Animal Models ◽

Meta Analysis ◽

Mean Difference ◽

Extracorporeal Shockwave Therapy ◽

Extracorporeal Shockwave ◽

Shockwave Therapy ◽

Cord Injury

Background As there is no consensus over the efficacy of extracorporeal shockwave therapy in the management of spinal cord injury complications, the current meta-analysis aims to investigate preclinical evidence on the matter. Methods The search strategy was developed based on keywords related to ‘spinal cord injury’ and ‘extracorporeal shockwave therapy’. A primary search was conducted in Medline, Embase, Scopus and Web of Science until the end of 2020. Studies which administered extracorporeal shockwave therapy on spinal cord injury animal models and evaluated motor function and/or histological findings were included. The standardised mean difference with a 95% confidence interval (CI) were calculated. Results Seven articles were included. Locomotion was significantly improved in the extracorporeal shockwave therapy treated group (standardised mean difference 1.68, 95% CI 1.05–2.31, P=0.032). It seems that the efficacy of extracorporeal shockwave therapy with an energy flux density of 0.1 mJ/mm2 is higher than 0.04 mJ/mm2 ( P=0.044). Shockwave therapy was found to increase axonal sprouting (standardised mean difference 1.31, 95% CI 0.65, 1.96), vascular endothelial growth factor tissue levels (standardised mean difference 1.36, 95% CI 0.54, 2.18) and cell survival (standardised mean difference 2.49, 95% CI 0.93, 4.04). It also significantly prevents axonal degeneration (standardised mean difference 2.25, 95% CI 1.47, 3.02). Conclusion Extracorporeal shockwave therapy significantly improves locomotor recovery in spinal cord injury animal models through neural tissue regeneration. Nonetheless, in spite of the promising results and clinical application of extracorporeal shockwave therapy in various conditions, current evidence implies that designing clinical trials on extracorporeal shockwave therapy in the management of spinal cord injury may not be soon. Hence, further preclinical studies with the effort to reach the safest and the most efficient treatment protocol are needed.

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Sinus Radiological Findings in General Asymptomatic Populations: A Systematic Review of Incidental Mucosal Changes

Otolaryngology ◽

10.1177/01945998211035097 ◽

2021 ◽

pp. 019459982110350

Author(s):

Basil Razi ◽

Adam Perkovic ◽

Raquel Alvarado ◽

Anna Stroud ◽

Jacqueline Ho ◽

...

Keyword(s):

Systematic Reviews ◽

Meta Analysis ◽

Population Groups ◽

Bibliographic Search ◽

Comprehensive Search ◽

Mucosal Changes ◽

Meta Analyses ◽

Asymptomatic Subjects ◽

Mucosal Thickening ◽

Retention Cysts

Objective To determine the range of incidental mucosal changes in a general sinonasally asymptomatic population on radiology. Data Sources Medline (1996-present) and Embase (1974-present) were searched on March 14, 2020, to identify articles that reported radiological sinus mucosal findings in asymptomatic population groups. Bibliographic search of included studies was conducted to identify additional articles. Review Methods The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and Cochrane Handbook for Systematic Reviews of Interventions. A comprehensive search strategy was formulated and articles screened to extract data reporting Lund-Mackay (LM) score, presence of mucous retention cysts, and maxillary mucosal thickening. A random-effects model was used in meta-analysis. Results A total of 950 articles were identified, of which 33 manuscripts met the inclusion criteria. The included studies involved 16,966 sinonasally asymptomatic subjects. The mean LM score was 2.24 (95% CI, 1.61-2.87), and an LM score of ≥4 in 14.71% (95% CI, 6.86-24.82%) was present across all general asymptomatic population groups. Mucous retention cysts were noted in 13% (95% CI, 8.33-18.55%) and maxillary mucosal thickening of ≥2 mm in 17.73% (95% CI, 8.67-29.08%). Conclusion The prevalence of incidental mucosal changes in a general asymptomatic population on radiology needs to be considered when making a diagnosis of chronic rhinosinusitis.

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Relevance of hMLH1 -93G>A, 655A>G and 1151T>A polymorphisms with colorectal cancer susceptibility: a meta-analysis based on 38 case-control studies

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.64.10.942 ◽

2018 ◽

Vol 64 (10) ◽

pp. 942-951 ◽

Cited By ~ 1

Author(s):

Mohammad Zare ◽

Jamal Jafari-Nedooshan ◽

Mohammadali Jafari ◽

Hossein Neamatzadeh ◽

Seyed Mojtaba Abolbaghaei ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Susceptibility ◽

Meta Analysis ◽

Asian Population ◽

Case Control ◽

Biomedical Literature ◽

Case Control Studies ◽

Increased Risk ◽

Comprehensive Search ◽

Meta Analyses

SUMMARY OBJECTIVE: There has been increasing interest in the study of the association between human mutL homolog 1 (hMLH1) gene polymorphisms and risk of colorectal cancer (CRC). However, results from previous studies are inconclusive. Thus, a meta-analysis was conducted to derive a more precise estimation of the effects of this gene. METHODS: A comprehensive search was conducted in the PubMed, EMBASE, Chinese Biomedical Literature databases until January 1, 2018. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. RESULTS: Finally, 38 case-control studies in 32 publications were identified met our inclusion criteria. There were 14 studies with 20668 cases and 19533 controls on hMLH1 −93G>A, 11 studies with 5,786 cases and 8,867 controls on 655A>G and 5 studies with 1409 cases and 1637 controls on 1151T>A polymorphism. The combined results showed that 655A>G and 1151T>A polymorphisms were significantly associated with CRC risk, whereas −93G>A polymorphism was not significantly associated with CRC risk. As for ethnicity, −93G>A and 655A>G polymorphisms were associated with increased risk of CRC among Asians, but not among Caucasians. More interestingly, subgroup analysis indicated that 655A>G might raise CRC risk in PCR-RFLP and HB subgroups. CONCLUSION: Inconsistent with previous meta-analyses, this meta-analysis shows that the hMLH1 655A>G and 1151T>A polymorphisms might be risk factors for CRC. Moreover, the −93G>A polymorphism is associated with the susceptibility of CRC in Asian population.

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Systematic review and meta-analyses of trendelenburg and prone position on intraocular pressure in adult patients undergoing surgery

10.32469/10355/70033 ◽

2019 ◽

Author(s):

◽

Sharon Ann Van Wicklin

Keyword(s):

Intraocular Pressure ◽

Prone Position ◽

Vision Loss ◽

Meta Analysis ◽

Adult Patients ◽

Trendelenburg Position ◽

Time Points ◽

Comprehensive Search ◽

Meta Analyses ◽

Difference Effect

Background. Patients undergoing surgery in the Trendelenburg and prone positions may be at risk for postoperative vision loss associated with increased intraocular pressure. The purpose of this dissertation research is to estimate the magnitude of the increase in intraocular pressure at specific perioperative time points in adult patients undergoing surgery in the Trendelenburg and prone positions. Methods. Comprehensive search strategies were used to identify eligible studies for two meta-analyses and to address the research questions. For each meta-analysis, standardized mean difference effect sizes were calculated for selected perioperative time points. Results. Using a random effects model, the meta-analysis examining the effect of Trendelenburg position, showed that intraocular pressure decreased significantly after induction and before arousal. Intraocular pressure increased significantly after abdominal insufflation and during Trendelenburg position. The meta-analysis examining the effect of prone position, showed that intraocular pressure increased significantly between induction of anesthesia and up to 10 minutes of prone position and continued to increase significantly until the end of the prone position. Conclusions. Intraocular pressure increases of the magnitude found in this research demonstrate the need for implementing interventions to reduce the risk for postoperative vision loss in patients undergoing surgery in the Trendelenburg and prone positions.

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Peptide hormone relaxin: from bench to bedside

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00276.2017 ◽

2018 ◽

Vol 314 (6) ◽

pp. R753-R760 ◽

Cited By ~ 8

Author(s):

Maria Jelinic ◽

Sarah A. Marshall ◽

Dennis Stewart ◽

Elaine Unemori ◽

Laura J. Parry ◽

...

Keyword(s):

Clinical Trials ◽

Animal Models ◽

Animal Studies ◽

Ischemia Reperfusion ◽

Peptide Hormone ◽

The Body ◽

Cervical Ripening ◽

Matrix Remodeling ◽

Vitro Fertilization

The peptide hormone relaxin has numerous roles both within and independent of pregnancy and is often thought of as a “pleiotropic hormone.” Relaxin targets several tissues throughout the body, and has many functions associated with extracellular matrix remodeling and the vasculature. This review considers the potential therapeutic applications of relaxin in cervical ripening, in vitro fertilization, preeclampsia, acute heart failure, ischemia-reperfusion, and cirrhosis. We first outline the animal models used in preclinical studies to progress relaxin into clinical trials and then discuss the findings from these studies. In many cases, the positive outcomes from preclinical animal studies were not replicated in human clinical trials. Therefore, the focus of this review is to evaluate the various animal models used to develop relaxin as a potential therapeutic and consider the limitations that must be addressed in future studies. These include the use of human relaxin in animals, duration of relaxin treatment, and the appropriateness of the clinical conditions being considered for relaxin therapy.

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Large-scale randomized evidence: Trials and meta-analyses of trials

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0010 ◽

2020 ◽

pp. 51-66

Author(s):

Colin Baigent ◽

Richard Peto ◽

Richard Gray ◽

Natalie Staplin ◽

Sarah Parish ◽

...

Keyword(s):

Clinical Trials ◽

Large Scale ◽

Meta Analysis ◽

False Negative ◽

Premature Deaths ◽

Common Causes ◽

The Common ◽

Meta Analyses ◽

Positive Results

Clinical trials generally need to be able to detect or to refute realistically moderate (but still worthwhile) differences between treatments in long-term disease outcome. Large-scale randomized evidence should be able to detect such effects, but medium-sized trials or medium-sized meta-analyses can, and often do, yield false-negative or exaggeratedly positive results. Hundreds of thousands of premature deaths each year could be avoided by seeking appropriately large-scale randomized evidence about various widely practicable treatments for the common causes of death, and by disseminating this evidence appropriately. This chapter takes a look at the use of large-scale randomized evidence—produced from trials and meta-analysis of trials—and how this data should be handled in order to produce accurate result.

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Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)

Systematic Reviews ◽

10.1186/s13643-020-01516-1 ◽

2020 ◽

Vol 9 (1) ◽

Author(s):

Steven Kwasi Korang ◽

Sophie Juul ◽

Emil Eik Nielsen ◽

Joshua Feinberg ◽

Faiza Siddiqui ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Individual Patient Data ◽

Viral Vector ◽

Meta Analysis ◽

Risk Of Bias ◽

Serious Adverse Events ◽

Meta Analyses ◽

Harmful Effects

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19. Methods/design We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately. Discussion COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease. Systematic review registration PROSPERO CRD42020196492

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The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies

Biomedicines ◽

10.3390/biomedicines8090355 ◽

2020 ◽

Vol 8 (9) ◽

pp. 355

Author(s):

Coralina Bernuy-Guevara ◽

Hassib Chehade ◽

Yannick D. Muller ◽

Julien Vionnet ◽

François Cachat ◽

...

Keyword(s):

Clinical Trials ◽

Meta Analysis ◽

Atypical Hemolytic Uremic Syndrome ◽

Real Life ◽

Kidney Injury ◽

Complement Component ◽

Kidney Transplant Recipients ◽

Antibody Mediated Rejection ◽

Esterase Inhibitors ◽

Meta Analyses

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common “off-label” (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.

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