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Biomedicine & Pharmacotherapy =... Mar 2022As the important active ingredients of Astragali Radix (AR), Astragalus polysaccharides (APs) have therapeutic potential for multiple diseases including nervous system...
As the important active ingredients of Astragali Radix (AR), Astragalus polysaccharides (APs) have therapeutic potential for multiple diseases including nervous system diseases, cardiovascular diseases, diabetes mellitus, and cancer. A large number of cell experiments combined with animal experiments have shed light on the therapeutic mechanisms and therapeutic effects of APs on a variety of diseases. However, the clinical application of APs is not widespread, except for the use of injected APs in the clinical adjuvant therapy of cancer. Due to the excessive molecular weight, bulky, low solubility and negatively charged characteristics, APs have low bioavailability which limits their clinical application. With the deepening of researches on the pharmaceutics of APs, the nanocrystals and moderate structural modification enormously boost the bioavailability, which may expand the application of APs. This review summarizes the studies in pharmacodynamic properties and pharmaceutics of APs, with the purpose of providing experimental researches and clinical application data for expanding the clinical development through expounding the therapeutic mechanisms and pharmaceutical researches of APs.
Topics: Animals; Astragalus Plant; Cardiovascular Diseases; Chemistry, Pharmaceutical; Diabetes Mellitus; Gastrointestinal Microbiome; Humans; Hypoxia; Immune Checkpoint Proteins; Immune System Diseases; Metabolic Diseases; Molecular Weight; Nanoparticles; Neoplasms; Neurodegenerative Diseases; Oxidative Stress; Polysaccharides
PubMed: 35086031
DOI: 10.1016/j.biopha.2022.112654 -
International Journal of Environmental... Dec 2021Parkinson's Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia.... (Review)
Review
Parkinson's Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia. Other non-motor symptoms include pain, depression, anxiety, and psychosis. This disease affects up to ten million people worldwide. The pathophysiology behind PD is due to the neurodegeneration of the nigrostriatal pathway. There are many conventional drugs used in the treatment of PD. However, there are limitations associated with conventional drugs. For instance, levodopa is associated with the on-off phenomenon, and it may induce wearing off as time progresses. Therefore, this review aimed to analyze the newly approved drugs by the United States-Food and Drug Administration (US-FDA) from 2016-2019 as the adjuvant therapy for the treatment of PD symptoms in terms of efficacy and safety. The new drugs include safinamide, istradefylline and pimavanserin. From this review, safinamide is considered to be more efficacious and safer as the adjunct therapy to levodopa as compared to istradefylline in controlling the motor symptoms. In Study 016, both safinamide 50 mg ( = 0.0138) and 100 mg ( = 0.0006) have improved the Unified Parkinson's Disease Rating Scale (UPDRS) part III score as compared to placebo. Improvement in Clinical Global Impression-Change (CGI-C), Clinical Global Impression-Severity of Illness (CGI-S) and off time were also seen in both groups of patients following the morning levodopa dose. Pimavanserin also showed favorable effects in ameliorating the symptoms of Parkinson's Disease Psychosis (PDP). A combination of conventional therapy and non-pharmacological treatment is warranted to enhance the well-being of PD patients.
Topics: Antiparkinson Agents; Humans; Levodopa; Parkinson Disease; Pharmaceutical Preparations; Psychotic Disorders; United States
PubMed: 35010624
DOI: 10.3390/ijerph19010364 -
Pain Research & Management 2022To assess if the addition of fentanyl to brachial plexus block has an impact on anesthetic outcomes and complication rates in patients undergoing upper extremity... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess if the addition of fentanyl to brachial plexus block has an impact on anesthetic outcomes and complication rates in patients undergoing upper extremity surgeries.
METHODS
We explore the PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases for all randomized controlled trials (RCTs) comparing adjuvant fentanyl with placebo/no drug for patients undergoing upper extremity surgery under brachial plexus block. Outcomes assessed were onset, duration of sensory and motor anesthesia, complications, and postoperative analgesia scores. Meta-analysis was conducted utilizing a random-effects model. The risk of bias was assessed using the Cochrane Collaboration's risk of bias assessment tool 2. Certainty of evidence was assessed using GRADE. Subgroup analysis was conducted depending upon the approach of brachial plexus block and type of local anesthetic.
RESULTS
Twelve RCTs with 660 patients were included. Addition of fentanyl had no effect on onset of sensory anesthesia (11 studies; MD: 0.48; 95% CI: -1.81, 0.85; = 96%; =0.48) but significantly shortened onset of motor anesthesia (8 studies; MD: -2.36; 95% CI: -3.99, -0.74; = 96%; =0.48). Duration of sensory anesthesia (9 studies; MD: 82.81; 95% CI: 41.81, 123.81; = 99%; < 0.0001) and motor anesthesia (7 studies; MD: 93.41; 95% CI: 42.35, 144.46; = 99%; =0.0003) was significantly increased with addition of fentanyl. The certainty of evidence-based on GRADE was deemed to be moderate for both onset and duration of anesthesia. The incidence of overall complications (nausea/vomiting and pruritis) was significantly higher in the fentanyl group (7 studies; OR: 2.14; 95% CI: 1.04, 4.40; = 8%; =0.04) but with low certainty of evidence.
CONCLUSIONS
Adjuvant fentanyl with brachial plexus block improves the onset of motor anesthesia but not sensory anesthesia. The duration of both sensory and motor anesthesia is significantly prolonged with fentanyl by around 83-93 minutes. However, clinicians should be aware that complications such as nausea/vomiting and pruritis are increased twofold with the addition of the drug. Current evidence is limited risk of bias in the RCTs and high heterogeneity in the meta-analyses.
Topics: Adjuvants, Pharmaceutic; Anesthetics, Local; Brachial Plexus Block; Fentanyl; Humans; Upper Extremity
PubMed: 35345625
DOI: 10.1155/2022/8704569 -
Toxins Apr 2023Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to... (Review)
Review
Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to complications such as dermonecrosis, myonecrosis, and even amputations. This systematic review aims to evaluate scientific evidence on therapies used to target local effects caused by envenomation. The PubMed, MEDLINE, and LILACS databases were used to perform a literature search on the topic. The review was based on studies that cited procedures performed on local injuries following envenomation with the aim of being an adjuvant therapeutic strategy. The literature regarding local treatments used following envenomation reports the use of several alternative methods and/or therapies. The venomous animals found in the search were snakes (82.05%), insects (2.56%), spiders (2.56%), scorpions (2.56%), and others (jellyfish, centipede, sea urchin-10.26%). In regard to the treatments, the use of tourniquets, corticosteroids, antihistamines, and cryotherapy is questionable, as well as the use of plants and oils. Low-intensity lasers stand out as a possible therapeutic tool for these injuries. Local complications can progress to serious conditions and may result in physical disabilities and sequelae. This study compiled information on adjuvant therapeutic measures and underscores the importance of more robust scientific evidence for recommendations that act on local effects together with the antivenom.
Topics: Animals; Antivenins; Snakes; Scorpions; Insecta; Spiders; Snake Bites
PubMed: 37235348
DOI: 10.3390/toxins15050313 -
Anticancer Research Oct 2023Using statins as antitumor agents is an approach to cancer therapy that has been explored extensively in specific cancer types. Reframing the query to how a statin... (Review)
Review
BACKGROUND/AIM
Using statins as antitumor agents is an approach to cancer therapy that has been explored extensively in specific cancer types. Reframing the query to how a statin interacts with the treatment regimen instead might provide new insight. Given that cell-cycle regulation influences tumorigenesis, it is possible that the cell-cycle phase which a given chemotherapy acts on influences the synergistic effects with adjuvant statin use. In this review, we outline the effect of statins in combination with chemotherapeutic drugs in in vivo animal model studies based on the class of chemotherapy and its relation to the cell cycle.
MATERIALS AND METHODS
This systematic review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 with 23 articles deemed eligible to be included.
RESULTS
Our review suggests that statins influence the success of chemotherapy treatments. Furthermore, enhanced efficacy was demonstrated with chemotherapeutic drugs that act at every phase of the cell cycle.
CONCLUSION
This type of compilation departs from the norm of describing statin influence on named cancer subtypes and instead catalogs how statins interact with categorical chemotherapy agents which might be beneficial for broader therapeutic decision-making across cancer subtypes, possibly contributing to pharmaceutical development, and thereby helping to maximize patient outcomes.
Topics: Animals; Mice; Antineoplastic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 37772570
DOI: 10.21873/anticanres.16621 -
F1000Research 2022A systematic review of clinical trials conducted with a low-dose inactivated influenza vaccine adjuvanted by azoximer bromide (AZB, Polyoxidonium), was performed to...
A systematic review of clinical trials conducted with a low-dose inactivated influenza vaccine adjuvanted by azoximer bromide (AZB, Polyoxidonium), was performed to compare vaccine reactogenicity against non-adjuvant vaccines. We also assessed whether lower amounts of antigen per viral strain in AZB-adjuvanted vaccines affected antibody responses. A robust search strategy identified scientific publications reporting 30 clinical trials, comprising data on 11,736 participants and 86 trial arms, for inclusion in the analysis. Local reaction rates (R ) appeared to be lower in AZB-adjuvanted vaccine treatment arms versus comparator vaccine treatment arms. Post-vaccination geometric mean titres in those exposed to AZB-adjuvanted vaccine and comparator vaccine treatment arms were similar in both children and adults aged 18-60 years, implying an antigen-sparing effect by AZB. Meta‑regression analysis based on a literature search of records or reports of clinical trials featuring AZB and the inactivated subunit of influenza published between 1998-2018 was conducted online in January 2019 and updated in August 2019. This search covered trials performed between 1993 and 2016 and suggested that AZB did not contribute to vaccine reactogenicity.
Topics: Adult; Child; Humans; Influenza Vaccines; Influenza, Human; Antibodies, Viral; Polymers; Adjuvants, Immunologic; Vaccines, Inactivated; Vaccines, Subunit
PubMed: 36176546
DOI: 10.12688/f1000research.75869.2 -
Scandinavian Journal of Pain Apr 2023A growing worldwide focus on opioid-free anaesthesia entails multimodal analgesic strategies involving non-opioids such as magnesium sulphate (MgSO). Several systematic... (Review)
Review
Is intravenous magnesium sulphate a suitable adjuvant in postoperative pain management? - A critical and systematic review of methodology in randomized controlled trials.
A growing worldwide focus on opioid-free anaesthesia entails multimodal analgesic strategies involving non-opioids such as magnesium sulphate (MgSO). Several systematic reviews have concluded there is beneficial analgesic effect of MgSO administration but do not take considerable heterogeneity among the studies into consideration. Medical literature published until June 2021 was searched in PubMed/Medline, Embase, Central and Web of Science: The final search yielded a total of 5,672 articles. We included only randomised controlled trials assessing the effect of intravenous MgSO on opioid consumption and acute postoperative pain when compared to either placebo or standardized analgesic treatment. The primary aim was to compare the homogeneity of essential variables and confounders. A post-hoc meta-analysis demonstrated a reduction in both postoperative morphine consumption (-6.12 mg) and pain score (-12.32 VAS points) in favour of the MgSO-groups. Data for meta-analysis was missing from 19 studies (45%) on morphine consumption and 29 studies (69%) for pain score, the majority of which reports no effect for either morphine consumption or pain score. The calculated heterogeneity among the included studies was considerable for both outcomes; =91% for morphine consumption and =96% for pain score. Although we found a per se reduction in opioid consumption and pain score, methodological heterogeneity and clinical shortcomings of pre-, intra-, and post anaesthetic data precludes conclusions on clinical importance of intraoperative intravenous MgSO. In addition, the reduction is likely less than what can be gained from using standardized analgesic treatment.
Topics: Humans; Adjuvants, Pharmaceutic; Analgesics; Analgesics, Opioid; Magnesium Sulfate; Morphine; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 36473053
DOI: 10.1515/sjpain-2022-0048 -
The Journal of Maternal-fetal &... Sep 2020To assess the additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) therapy in preventing recurrent spontaneous preterm birth in women with an... (Meta-Analysis)
Meta-Analysis
To assess the additional benefits of 17-hydroxyprogesterone caproate (17-OHPC) therapy in preventing recurrent spontaneous preterm birth in women with an ultrasound-indicated cerclage. Electronic databases (Medline, Scopus, ClinicalTrials.gov, PROSPERO, Embase, Scielo, and the Cochrane Central Register of Controlled Trials) were searched for studies published before September 2018. Keywords included "preterm birth", "ultrasound-indicated cerclage", "pregnancy" and "17-hydroxyprogesterone caproate". Studies comparing ultrasound-indicated cerclage alone to cerclage plus 17-OHPC were included. The primary outcome measure was preterm birth at <35 weeks of gestation. Secondary outcome measures include preterm birth <24 weeks, <28 weeks, <32 weeks and <37 weeks of gestation, necrotizing enterocolitis (NEC), fetal birth weight, and intraventricular hemorrhage (grades III and IV). Meta-analysis was performed using the random effects model of DerSimonian and Laird. Risk of bias and quality assessment was performed using the risk of bias in nonrandomized studies of interventions (ROBINS-I). Four studies met inclusion criteria and were included in the final analysis. Of the 396 women who received ultrasound-indicated cerclage, 142 (35.9%) received adjuvant 17-OHPC. The primary outcome, preterm birth <35 weeks of gestation, was present in three studies and 332/396 singleton pregnancies. Though there was a trend towards a reduced risk of preterm birth, the summary estimate of effect was not statistically significant when comparing cerclage alone to cerclage plus 17-OHPC at <35 weeks (relative risk (RR) 0.95, 95% CI 0.77-1.17). Similarly, we found no differences in preterm birth at <24 weeks (RR 0.30, 95% CI 0.06-1.60), <28 weeks (RR 0.57, 95% CI 0.13-2.53), and <32 weeks (RR 0.99, 95% CI 0.44-2.27) when comparing cerclage alone to cerclage plus 17-OHPC. There were no differences in fetal birth weight, intraventricular hemorrhage and necrotizing enterocolitis comparing cerclage alone to cerclage plus 17-OHPC. Intramuscular 17-OHPC in combination with ultrasound-indicated cerclage in women with prior preterm birth had no additional effect in reducing spontaneous recurrent preterm birth or improving perinatal outcomes.
Topics: 17 alpha-Hydroxyprogesterone Caproate; 17-alpha-Hydroxyprogesterone; Adjuvants, Pharmaceutic; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Pregnancy; Premature Birth
PubMed: 30626240
DOI: 10.1080/14767058.2019.1568406 -
Sexually Transmitted Infections Dec 2023The main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE associated with timing of human papillomavirus (HPV) vaccination using data from published studies.
DESIGN
Meta-analysis and meta-regression.
DATA SOURCES
A computerised literature search was undertaken using the MEDLINE, EMBASE, International Pharmaceutical Abstracts, Derwent Drug File, ProQuest Science and Technology, Cochrane and MedRxiv databases. To be eligible, the studies, with no language restrictions, had to be published between 1 January 2001 and 25 May 2023.
REVIEW METHODS
Included were studies with an unvaccinated reference group that assessed CIN2+ recurrence irrespective of the HPV genotype in women undergoing conisation provided. The present study was carried out in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines. The risk of study bias was assessed using the Newcastle-Ottawa Quality Assessment Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Data synthesis was conducted using meta-analysis and meta-regression.
RESULTS
Out of a total of 14 322 publications, 20 studies with a total of 21 estimates were included. The overall VE against recurrent CIN2+ irrespective of the HPV genotype achieved 69.5% (95% CI: 54.7% to 79.5%). While the HPV vaccine valency, follow-up duration, type of study including its risk of bias had no effect on VE, the highest VE of 78.1% (95% CI: 68.7% to 84.7%) was reported for women receiving their first dose not earlier than the day of excision. This outcome was supported by additional analyses and a VE prediction interval ranging from 67.1% to 85.4%.
CONCLUSIONS
The outcome of this meta-analysis and meta-regression convincingly showed the beneficial effect of post-excisional HPV vaccination against CIN2+ recurrence. Studies published to date have been unable to determine whether or not vaccination, completed or initiated before conisation, would be associated with more favourable results.
PROSPERO REGISTRATION NUMBER
CRD42022353530.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomavirus Infections; Uterine Cervical Dysplasia; Vaccination; Papillomavirus Vaccines
PubMed: 37553234
DOI: 10.1136/sextrans-2023-055793 -
Frontiers in Immunology 2023Effect of renin-angiotensin-aldosterone system inhibitors (RAASIs) in combination with immune checkpoint inhibitors (ICIs) on prognoses in cancer patients remains... (Meta-Analysis)
Meta-Analysis
Effect of renin-angiotensin-aldosterone system inhibitors on survival outcomes in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.
BACKGROUND
Effect of renin-angiotensin-aldosterone system inhibitors (RAASIs) in combination with immune checkpoint inhibitors (ICIs) on prognoses in cancer patients remains controversial. This study systematically evaluated the effect of RAASIs on survival outcomes in cancer patients receiving ICIs treatment and provided an evidence-based reference for the rational use of RAASIs and ICIs combination therapy in clinical practice.
METHODS
Studies evaluating the prognosis of RAASIs-used versus RAASIs-free in cancer patients receiving ICIs treatment from inception to 1 November 2022 were retrieved by searching PubMed, Cochrane Library, Web of Science, Embase, and major conference proceedings. Studies in English reporting hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS) were included. Statistical analyses were conducted using the software Stata 17.0.
RESULTS
A total of 12 studies containing 11739 patients were included, comprising ~4861 patients in the RAASIs-used and ICIs-treated group and ~6878 patients in RAASIs-free and ICIs-treated group. The pooled HR was 0.85 (95%CI, 0.75-0.96; = 0.009) for OS and 0.91 (95%CI, 0.76-1.09; = 0.296) for PFS, indicating a positive effect of RAASIs concomitant with ICIs on cancer patients. This effect was observed especially in patients with urothelial carcinoma (HR, 0.53; 95%CI, 0.31-0.89; = 0.018) and renal cell carcinoma (HR, 0.56; 95%CI, 0.37-0.84; = 0.005) on OS.
CONCLUSION
Concomitant use of RAASIs and ICIs enhanced the efficacy of ICIs and this combination regimen was associated with significantly improved OS and a trend towards better PFS. RAASIs can be considered as adjuvant drugs when hypertensive patients receive ICIs treatment. Our results provide an evidence-based reference for the rational use of the RAASIs and ICIs combination therapy to improve the efficacy of ICIs in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022372636; https://inplasy.com/, identifier INPLASY2022110136.
Topics: Humans; Immune Checkpoint Inhibitors; Carcinoma, Transitional Cell; Renin-Angiotensin System; Urinary Bladder Neoplasms; Kidney Neoplasms
PubMed: 37153578
DOI: 10.3389/fimmu.2023.1155104