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Indian Journal of Pharmacology 2021Registration of study protocols brings about transparency and traceability and the amount of publication bias can be estimated. In this study, we have collected and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Registration of study protocols brings about transparency and traceability and the amount of publication bias can be estimated. In this study, we have collected and presented data regarding clinical study registries, preclinical, in vitro and in silico study registries across the globe.
MATERIALS AND METHODS
We searched via Google Search Engine with appropriate keywords e.g. name of country (n = 198), name of continent (n = 7), registry, study registry, animal, in silico, virtual, simulation, preclinical, animal, clinical trial. The overall pooled prevalence of clinical study registries and WHO primary registries in per continent was calculated using Medcalc software.
RESULTS
The overall pooled prevalence of clinical study registries were 13% in each continent. The prevalence of WHO primary study registries were 8.9% of the countries per continent. Overall, there are 17 primary registries associated with WHO ICTRP as primary registries, 2 partner registries and 6 registries are affiliated to ICMJE. However, the amount of preclinical animal study registry was quite less (n = 4). Regarding in vitro studies, only country specific in vitro fertilization registries were available, however, in other research domains, registries were absent. Only one simulation study registry was available.
CONCLUSION
At priori study registration is essential to deal with selective reporting. Comparison between study protocol and final report allows us to know the protocol deviations and allows us to evaluate risk of bias and internal validity of the research findings. Although trialists are responsible for the completeness of records, yet the registries must have some measures for their periodic update and quality control of the data.
Topics: Animals; Clinical Protocols; Clinical Trials as Topic; Drug Evaluation, Preclinical; Humans; Registries; World Health Organization
PubMed: 34100401
DOI: 10.4103/ijp.ijp_1090_20 -
International Journal of Molecular... Jul 2023Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and... (Review)
Review
Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and potentially serving as a therapeutic agent for chronic inflammatory diseases. The aim of this review was to systematically investigate preclinical and clinical studies on maresin to inform translational research. Two independent reviewers performed comprehensive searches with the term "Maresin (NOT) Review" on PubMed. A total of 137 studies were included and categorized into 11 human organ systems. Data pertinent to clinical translation were specifically extracted, including delivery methods, optimal dose response, and specific functional efficacy. Maresins generally exhibit efficacy in treating inflammatory diseases, attenuating inflammation, protecting organs, and promoting tissue regeneration, mostly in rodent preclinical models. The nervous system has the highest number of original studies ( = 25), followed by the cardiovascular system, digestive system, and respiratory system, each having the second highest number of studies ( = 18) in the field. Most studies considered systemic delivery with an optimal dose response for mouse animal models ranging from 4 to 25 μg/kg or 2 to 200 ng via intraperitoneal or intravenous injection respectively, whereas human in vitro studies ranged between 1 and 10 nM. Although there has been no human interventional clinical trial yet, the levels of MaR1 in human tissue fluid can potentially serve as biomarkers, including salivary samples for predicting the occurrence of cardiovascular diseases and periodontal diseases; plasma and synovial fluid levels of MaR1 can be associated with treatment response and defining pathotypes of rheumatoid arthritis. Maresins exhibit great potency in resolving disease inflammation and bridging tissue regeneration in preclinical models, and future translational development is warranted.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Chronic Disease; Docosahexaenoic Acids; Inflammation; Macrophages
PubMed: 37446190
DOI: 10.3390/ijms241311012 -
Clinical Rheumatology Jan 2022Corticosteroid-sparing disease-modifying anti-rheumatic drugs are an area of active exploration in large vessel vasculitis (LVV), i.e., Takayasu arteritis (TAK) and... (Review)
Review
Corticosteroid-sparing disease-modifying anti-rheumatic drugs are an area of active exploration in large vessel vasculitis (LVV), i.e., Takayasu arteritis (TAK) and Giant Cell Arteritis (GCA). The role of Janus kinase (JAK) inhibitors has been recently identified in different inflammatory rheumatic diseases. We conducted a systematic review of the use of JAK inhibitors in LVV across MEDLINE, Scopus, Web of Science, EMBASE, PubMed Central, Cochrane database of controlled trials, clinicaltrials.gov, and major recent international conferences. We identified four cohort studies and ten case reports. The JAK inhibitors used in these studies were tofacitinib, baricitinib, and ruxolitinib. A cohort study in TAK compared 27 patients treated with tofacitinib with 26 others treated with methotrexate, with better clinical outcomes with tofacitinib but similar angiographic stabilization, relapses, corticosteroid-sparing effect, and adverse events in both groups. Most of the other studies favored clinical responses with JAK inhibitors in LVV but with a paucity of data on other outcomes. Most of the included studies were of moderate quality. Evidence from pre-clinical models of LVV as well as limited in vivo data in patients with TAK appears to suggest that JAK inhibition reduces adventitial fibrosis, intimal proliferation, and inflammatory T lymphocyte infiltration in the media as well as reduces resident memory T cells in the vascular wall (which are otherwise resistant to corticosteroids). Ongoing clinical trials of tofacitinib, baricitinib, and upadacitinib in LVV shall help to further clarify the potential promise of JAK inhibitors for LVV (PROSPERO registration number CRD42021273359). KEY POINTS : •Tofacitinib appeared to associate with better clinical outcomes than methotrexate in TAK. •JAKinibs reduce adventitial fibrosis, intimal proliferation, and inflammatory vascular infiltrate in pre-clinical models of LVV. •Tofacitinib downregulates resident memory vascular T lymphocytes in pre-clinical models of LVV.
Topics: Antirheumatic Agents; Cohort Studies; Giant Cell Arteritis; Humans; Janus Kinase Inhibitors; Memory T Cells; Takayasu Arteritis
PubMed: 34729652
DOI: 10.1007/s10067-021-05973-4 -
Journal of Lasers in Medical Sciences 2022While a wound caused by a minor cutaneous incision routinely heals in a short time, wounds from major surgical operations might need numerous days to heal and may leave... (Review)
Review
While a wound caused by a minor cutaneous incision routinely heals in a short time, wounds from major surgical operations might need numerous days to heal and may leave an obvious cicatrix. The use of blue light therapy (BLT) to destroy infectious microorganisms and disrupt biofilm formation could be an efficient method for healing ulcers. This systematic review focused on the effects of BLT in different preclinical studies and clinical models of skin wound healing. Furthermore, this study attempted to determine what main light parameters should be tested in preclinical and clinical studies. The online databases PubMed.gov, Google Scholar, Scopus, Web of Science, and Cochrane were searched using the keywords "blue light" and "wound healing" according to PRISMA guidelines. No publication time limit was enforced. A total of 858 articles were identified, and 17 articles in three distinct categories were included for review. They comprised two articles on humans, fourteen articles on healthy animals, and one article on diabetic animals. Some studies have shown that the application of BLT on preclinical and clinical models of wound healing is able to significantly accelerate the healing process. Few studies, however, have explored the bactericidal effect of BLT on skin injury repair in burn patients. Further preclinical investigations designed to provide a better understanding of the bactericidal effect of BLT using standardized protocols, different BLT wavelengths, and different stages of the wound healing process of infected wounds and ulcers in healthy and diabetic animals should be carried out before clinical trials can be considered. BLT could eventually be a good option for treating infected chronic wounds, including those in diabetic patients.
PubMed: 37041783
DOI: 10.34172/jlms.2022.69 -
Pain Apr 2020Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and... (Meta-Analysis)
Meta-Analysis
Despite large efforts to test analgesics in animal models, only a handful of new pain drugs have shown efficacy in patients. Here, we report a systematic review and meta-analysis of preclinical studies of the commercially successful drug pregabalin. Our primary objective was to describe design characteristics and outcomes of studies testing the efficacy of pregabalin in behavioral models of pain. Secondarily, we examined the relationship between design characteristics and effect sizes. We queried MEDLINE, Embase, and BIOSIS to identify all animal studies testing the efficacy of pregabalin published before January 2018 and recorded experimental design elements addressing threats to validity and all necessary data for calculating effect sizes, expressed as the percentage of maximum possible effect. We identified 204 studies (531 experiments) assessing the efficacy of pregabalin in behavioral models of pain. The analgesic effect of pregabalin was consistently robust across every etiology/measure tested, even for pain conditions that have not responded to pregabalin in patients. Experiments did not generally report using design elements aimed at reducing threats to validity, and analgesic activity was typically tested in a small number of model systems. However, we were unable to show any clear relationships between preclinical design characteristics and effect sizes. Our findings suggest opportunities for improving the design and reporting of preclinical studies in pain. They also suggest that factors other than those explored in this study may be more important for explaining the discordance between outcomes in animal models of pain and those in clinical trials.
Topics: Analgesics; Animals; Humans; Pain; Pregabalin
PubMed: 31977931
DOI: 10.1097/j.pain.0000000000001749 -
Drugs Feb 2022Gliomas represent most common primary brain tumors. Glioblastoma (GBM) is the most common subtype and carries a poor prognosis. There is growing interest in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gliomas represent most common primary brain tumors. Glioblastoma (GBM) is the most common subtype and carries a poor prognosis. There is growing interest in the anti-glioma properties of statins. The aim of this study was to conduct a systematic review of the preclinical literature and to meta-analyze existing clinical studies to determine what benefit, if any, statins may confer in the context of glioma.
METHODS
The PubMed, Embase, Cochrane, and Web of Science libraries were queried in May 2021. Preclinical studies were included if they investigated the anti-cancer effects of statins in glioma in vitro and in vivo. Clinical studies were included if they reported incidence rates of glioma by statin use, or mortality outcomes among GBM patients by statin use. Pooled point estimates were calculated using a random-effects model.
RESULTS
In total, 64 publications, 51 preclinical and 13 clinical, were included. Preclinical studies indicated that statins inhibited glioma cell proliferation, migration, and invasion. These effects were time- and concentration-dependent. Synergistic anti-glioma effects were observed when statins were combined with other anti-cancer therapies. Clinical observational studies showed an inverse, albeit non-statistically significant, association between statin use and incidence rate of glioma (HR = 0.84, 95% CI 0.62-1.13, I = 72%, p-heterogeneity = 0.003, 6 studies). Statin use was not associated with better overall survival following GBM surgery (HR = 1.05, 95% CI 0.85-1.30, I = 30%, p-heterogeneity = 0.23, 4 studies).
CONCLUSION
Statins were potent anti-cancer drugs that suppressed glioma growth through various mechanisms in vitro; these effects have translated into the clinical realm, clinically but not statistically, in terms of glioma incidence but not GBM survival.
Topics: Antineoplastic Agents; Glioma; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 35122635
DOI: 10.1007/s40265-021-01668-x -
PloS One 2017B. anthracis anti-toxin agents are approved and included in the Strategic National Stockpile based primarily on animal infection trials. However, in the only anthrax... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
B. anthracis anti-toxin agents are approved and included in the Strategic National Stockpile based primarily on animal infection trials. However, in the only anthrax outbreak an approved anti-toxin agent was administered in, survival did not differ comparing recipients and non-recipients, although recipients appeared sicker.
OBJECTIVE
Employ a systematic review and meta-analysis to investigate preclinical studies supporting anthrax anti-toxin agents.
DATA SOURCE
PubMed, EMBASE, and Scopus.
STUDY ELIGIBILITY
Compared survival with an anti-toxin agent versus control in B. anthracis challenged, antibiotic treated animals.
STUDY METHODS
Examine model and study design and the effect of anti-toxin agents on relative risk of death(95%CI) (RR).
RESULTS
From 9 studies, 29 experiments were analyzed which included 4 species (748 animals) and 5 agents; LFI, AIG, AVP-21D9, Raxibacumab, and ETI-204. Only five experiments were blinded and no experiment included the cardiopulmonary support sick B. anthracis patients receive. Only one agent in a single un-blinded experiment reduced RR significantly [0.45(0.22,0.940]. However, in six studies testing an agent in more than one experiment in the same species, agents had consistent survival effects across experiments [I2 = 0, p≥0.55 in five and I2 = 42%, p = 0.16 in one]. Within each species, agents had effects on the side of benefit; in one study testing AVP-21D9 in mice [0.11(0.01,1.82)] or guinea pigs [0.70(0.48,1.03)]; across eight rabbit studies testing LFI, Raxibacumab, AIG or ETI-204 [0.62(0.45,0.87); I2 = 17.4%, p = 0.29]; and across three monkey studies testing Raxibacumab, AIG or ETI-204 [0.66(0.34,1.27); I2 = 25.3%, p = 0.26]. Across all agents and species, agents decreased RR [0.64(0.52,0.79); I2 = 5.3%, p = 0.39].
LIMITATIONS
Incidence of selective reporting not identifiable.
CONCLUSIONS
Although overall significant, individually anti-toxin agents had weak beneficial effects. Lack of study blinding and relevant clinical therapies further weakened studies. Although difficult, preclinical studies with more robust designs and results are warranted to justify the resources necessary to maintain anti-toxin agents in national stockpiles.
Topics: Animals; Anthrax; Anti-Bacterial Agents; Antigens, Bacterial; Antitoxins; Bacillus anthracis; Disease Models, Animal; Humans; Research Design; Treatment Outcome
PubMed: 28797061
DOI: 10.1371/journal.pone.0182879 -
Neurosurgical Review Apr 2021Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit...
Given the median survival of 15 months after diagnosis, novel treatment strategies are needed for glioblastoma. Beta-blockers have been demonstrated to inhibit angiogenesis and tumor cell proliferation in various cancer types. The aim of this study was to systematically review the evidence on the effect of beta-blockers on glioma growth. A systematic literature search was performed in the PubMed, Embase, Google Scholar, Web of Science, and Cochrane Central to identify all relevant studies. Preclinical studies concerning the pharmacodynamic effects of beta-blockers on glioma growth and proliferation were included, as well as clinical studies that studied the effect of beta-blockers on patient outcomes according to PRISMA guidelines. Among the 980 citations, 10 preclinical studies and 1 clinical study were included after title/abstract and full-text screening. The following potential mechanisms were identified: reduction of glioma cell proliferation (n = 9), decrease of glioma cell migration (n = 2), increase of drug sensitivity (n = 1), induction of glioma cell death (n = 1). Beta-blockers affect glioma proliferation by inducing a brief reduction of cAMP and a temporary cell cycle arrest in vitro. Contrasting results were observed concerning glioma cell migration. The identified clinical study did not find an association between beta-blockers and survival in glioma patients. Although preclinical studies provide scarce evidence for the use of beta-blockers in glioma, they identified potential pathways for targeting glioma. Future studies are needed to clarify the effect of beta-blockers on clinical endpoints including survival outcomes in glioma patients to scrutinize the value of beta-blockers in glioma care.
Topics: Adrenergic beta-Antagonists; Brain Neoplasms; Cell Death; Cell Proliferation; Clinical Trials as Topic; Drug Evaluation, Preclinical; Glioblastoma; Glioma; Humans; Neovascularization, Pathologic
PubMed: 32172480
DOI: 10.1007/s10143-020-01277-4 -
Translational Stroke Research Oct 2023Cerebral cavernous malformation (CCM), either sporadic or familial, is a devastating vascular malformation affecting the central nervous system that can present with... (Review)
Review
Cerebral cavernous malformation (CCM), either sporadic or familial, is a devastating vascular malformation affecting the central nervous system that can present with intracerebral hemorrhage, seizure, and new focal neurologic deficits resulting in substantial morbidity and mortality. To date, there is no effective evidence-based preventive regimen. There have been several preclinical and clinical studies investigating the potential mechanisms and benefits of beta-blockers, especially on propranolol. We aimed to conduct a systematic review on the published literature investigating the use of beta-blockers in the treatment of CCM, including both preclinical and clinical studies between 2008 and 2023 using public databases. A total of 2 preclinical studies and 6 clinical studies met the inclusion/exclusion criteria and were included. Data was extracted and synthesized from 5 clinical studies for meta-analysis. The meta-analysis failed to demonstrate a statistically significant protective effect of beta-blockers in preventing intracerebral hemorrhage or developing focal neurologic deficits in subjects with CCM (overall effect = 0.78 (0.20, 3.11), p = 0.73). Overall, there was a paucity of high quality clinical trials, partially due to limited cases of CCM. Addressing this gap may require collaborative efforts at a national or international level. In this review, we summarized all barriers and opportunities on this topic. Additionally, we proposed establishing an evidence-based approach on the use of beta-blockers in preventing recurrent hemorrhage and focal neurological deficits in patients with CCM.
PubMed: 37857790
DOI: 10.1007/s12975-023-01199-5 -
Journal of Cachexia, Sarcopenia and... Feb 2024Patients with chronic kidney disease (CKD) are often regarded as experiencing wasting of muscle mass and declining muscle strength and function, collectively termed... (Meta-Analysis)
Meta-Analysis Review
Patients with chronic kidney disease (CKD) are often regarded as experiencing wasting of muscle mass and declining muscle strength and function, collectively termed sarcopenia. The extent of skeletal muscle wasting in clinical and preclinical CKD populations is unclear. We evaluated skeletal muscle atrophy in preclinical and clinical models of CKD, with multiple sub-analyses for muscle mass assessment methods, CKD severity, sex and across the different preclinical models of CKD. We performed a systematic literature review of clinical and preclinical studies that measured muscle mass/size using the following databases: Ovid Medline, Embase and Scopus. A random effects meta-analysis was utilized to determine standard mean difference (SMD; Hedges' g) between healthy and CKD. Heterogeneity was evaluated using the I statistic. Preclinical study quality was assessed via the Systematic Review Centre for Laboratory Animal Experimentation and clinical studies quality was assessed via the Newcastle-Ottawa Scale. This study was registered in PROSPERO (CRD42020180737) prior to initiation of the search. A total of 111 studies were included in this analysis using the following subgroups: 106 studies in the primary CKD analysis, 18 studies that accounted for diabetes and 7 kidney transplant studies. Significant atrophy was demonstrated in 78% of the preclinical studies and 49% of the clinical studies. The random effects model demonstrated a medium overall SMD (SMD = 0.58, 95% CI = 0.52-0.64) when combining clinical and preclinical studies, a medium SMD for the clinical population (SMD = 0.48, 95% CI = 0.42-0.55; all stages) and a large SMD for preclinical CKD (SMD = 0.95, 95% CI = 0.76-1.14). Further sub-analyses were performed based upon assessment methods, disease status and animal model. Muscle atrophy was reported in 49% of the clinical studies, paired with small mean differences. Preclinical studies reported significant atrophy in 78% of studies, with large mean differences. Across multiple clinical sub-analyses such as severity of CKD, dialysis modality and diabetes, a medium mean difference was found. Sub-analyses in both clinical and preclinical studies found a large mean difference for males and medium for females suggesting sex-specific implications. Muscle atrophy differences varied based upon assessment method for clinical and preclinical studies. Limitations in study design prevented conclusions to be made about the extent of muscle loss with disease progression, or the impact of dialysis. Future work would benefit from the use of standardized measurement methods and consistent clinical staging to improve our understanding of atrophy changes in CKD progression, and analysis of biological sex differences.
Topics: Humans; Female; Male; Renal Insufficiency, Chronic; Muscular Atrophy; Renal Dialysis; Muscle, Skeletal; Diabetes Mellitus
PubMed: 38062879
DOI: 10.1002/jcsm.13400