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Frontiers in Pharmacology 2023Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the...
Effects of early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies.
Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients. To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions. Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions. [https://www.crd.york.ac.uk/prospero/dis], identifier [CRD42022316327].
PubMed: 37214454
DOI: 10.3389/fphar.2023.1185277 -
World Journal of Urology Jul 2023To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC)... (Meta-Analysis)
Meta-Analysis
PURPOSE
To analyze and summarize the efficacy of immune checkpoint inhibitor (ICI) alone or in combination therapy for renal cell carcinoma (RCC) and urothelial carcinoma (UC) stratified by sex.
METHODS
Three databases were queried in October 2022 for randomized controlled trials (RCTs) analyzing RCC and UC patients treated with ICIs. We analyzed the association between sex and the efficacy of ICIs in RCC and UC patients across several clinical settings. The outcomes of interest were overall survival (OS) and progression-free survival for the metastatic setting and disease-free survival (DFS) for the adjuvant setting.
RESULTS
Overall, 16 RCTs were included for meta-analyses and network meta-analyses. In the first-line treatment of metastatic RCC (mRCC) and UC (mUC) patients, ICI-based combination therapies significantly improved OS compared to the current standard of care, regardless of sex. Adjuvant ICI monotherapy reduced the risk of disease recurrence in female patients with locally advanced RCC (pooled hazard ratio [HR]: 0.71, 95% confidence interval [CI] 0.55-0.93) but not in male patients, and, conversely, in male patients with muscle-invasive UC (pooled HR: 0.80, 95%CI 0.68-0.94) but not in female patients. Treatment ranking analyses in the first-line treatment of mRCC and mUC showed different results between sexes. Of note, regarding adjuvant treatment for RCC, pembrolizumab (99%) had the highest likelihood of improved DFS in males, whereas atezolizumab (84%) in females.
CONCLUSIONS
OS benefit of first-line ICI-based combination therapy was seen in mRCC and mUC patients regardless of sex. Sex-based recommendations for ICI-based regimens according to the clinical setting may help guide clinical decision-making.
Topics: Female; Male; Humans; Immune Checkpoint Inhibitors; Carcinoma, Renal Cell; Neoplasm Recurrence, Local; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Kidney; Adjuvants, Immunologic; Kidney Neoplasms
PubMed: 37209143
DOI: 10.1007/s00345-023-04412-0 -
The Journal of Clinical Endocrinology... Oct 2023Clinical trials have investigated the role of antiresorptive agents, including bisphosphonates and denosumab, in patients with primary breast cancer receiving adjuvant... (Meta-Analysis)
Meta-Analysis
The Clinical Benefits of Antiresorptive Agents in Patients with Primary Breast Cancer Receiving Adjuvant Endocrine Therapy: A Systematic Review with Pairwise and Network Meta-analysis.
CONTEXT
Clinical trials have investigated the role of antiresorptive agents, including bisphosphonates and denosumab, in patients with primary breast cancer receiving adjuvant endocrine therapy, aiming for better bone protection and/or improving survival.
OBJECTIVE
To summarize the clinical effects of antiresorptive agents in patients with early breast cancer receiving endocrine therapy.
METHODS
We systematically reviewed and synthesized the clinical benefits and harms of antiresorptive agents in patients with early breast cancer receiving endocrine therapy by calculating the risk ratios (RRs).
RESULTS
In the pooled meta-analysis, antiresorptive agents had significant clinical benefits on disease recurrence (RR 0.78, 95% CI 0.67-0.90) and locoregional recurrence (RR 0.69, 95% CI 0.49-0.95) in patients with breast cancer receiving endocrine therapy. Early use of antiresorptive agents has a beneficial effect on secondary endocrine therapy resistance instead of primary resistance. Safety analysis revealed that potential risk for osteonecrosis of the jaw (ONJ, RR 3.29, 95% CI 1.12-9.68) with antiresorptive agents; however, there is an insignificant difference in arthralgia. The subgroup analyses revealed that intervention with bisphosphonates might have profound clinical benefits, but also increased the occurrence of ONJ. A network meta-analysis further supported the clinical effects of early antiresorptive agent use compared with delayed use or placebo.
CONCLUSION
Using antiresorptive agents early in patients with breast cancer receiving adjuvant endocrine therapy may provide additional benefits in risk reduction of recurrence, but there is a potential risk of ONJ.
Topics: Humans; Female; Bone Density Conservation Agents; Denosumab; Breast Neoplasms; Network Meta-Analysis; Neoplasm Recurrence, Local; Diphosphonates
PubMed: 37170778
DOI: 10.1210/clinem/dgad247 -
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 -
The Cochrane Database of Systematic... Feb 2023Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains... (Review)
Review
BACKGROUND
Thalassaemia is a quantitative abnormality of haemoglobin caused by mutations in genes controlling production of alpha or beta globins. Abnormally unpaired globin chains cause membrane damage and cell death within organ systems and destruction of erythroid precursors in the bone marrow, leading to haemolytic anaemia. The life-long management of the general health effects of thalassaemia is highly challenging, and failure to deal with dental and orthodontic complications exacerbates the public health, financial and personal burden of the condition. There is a lack of evidence-based guidelines to help care seekers and providers manage such dental and orthodontic complications. This review aimed to evaluate the available evidence on methods for treating dental and orthodontic complications in people with thalassaemia to inform future recommendations. This is an update of a Cochrane Review first published in 2019.
OBJECTIVES
To assess different methods for treating dental and orthodontic complications in people with thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register in September 2022, and we searched nine online databases and trials registries in January 2022. We searched the reference lists of relevant articles and reviews and contacted haematologists, experts in fields of dentistry, organisations, pharmaceutical companies and researchers working in this field.
SELECTION CRITERIA
We searched for published or unpublished randomised controlled trials (RCTs) that evaluated treatment of dental and orthodontic complications in individuals diagnosed with thalassaemia, irrespective of phenotype, severity, age, sex and ethnic origin.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the 37,242 titles retrieved by the search. After deduplication, we identified two potentially relevant RCTs. On assessing their eligibility against our inclusion and exclusion criteria, we excluded one and included the other.
MAIN RESULTS
We included one parallel-design RCT conducted in Saudi Arabia and involving 29 participants (19 males, 10 females) with thalassaemia. It aimed to assess the effectiveness of photodynamic therapy as an adjuvant to conventional full-mouth ultrasonic scaling for the treatment of gingivitis. The average age of participants was around 23 years. There is very low-certainty evidence from this trial that full-mouth ultrasonic scaling plus photodynamic therapy compared to full-mouth ultrasonic scaling alone may improve gingival index score and bleeding on probing after 12 weeks in people with thalassaemia. We found no studies that assessed other interventions for the various dental or orthodontic complications of thalassaemia.
AUTHORS' CONCLUSIONS
Although the included study showed greater reduction in gingivitis in the group treated with full-mouth ultrasonic scaling plus photodynamic therapy, the evidence is of very low certainty. The study had unclear risk of bias, a short follow-up period and no data on safety or adverse effects. We cannot make definitive recommendations for clinical practice based on the limited evidence of a single trial. Future studies will very likely affect the conclusions of this review. This review highlights the need for high-quality RCTs that investigate the effectiveness of various treatment modalities for dental and orthodontic complications in people with thalassaemia. It is crucial that future trials assess adverse effects of interventions.
Topics: Male; Female; Humans; Thalassemia; Gingivitis
PubMed: 36732291
DOI: 10.1002/14651858.CD012969.pub3 -
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 -
Minerva Anestesiologica May 2023Elective cesarean section (CS) is usually performed using spinal anesthesia (SA), which requires the use of local anesthetic (LA) agents, commonly combined with adjuvant... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Elective cesarean section (CS) is usually performed using spinal anesthesia (SA), which requires the use of local anesthetic (LA) agents, commonly combined with adjuvant drugs. We performed a systematic review and meta-analysis aimed at studying the advantages of α-2 agonists as compared to fentanyl during SA for CS.
EVIDENCE ACQUISITION
We screened PubMed and EMBASE for randomized controlled trials (RCTs). We calculated the mean difference (MD) for continuous outcomes, and the relative risk for dichotomous outcomes, using a random-effect model with 95% confidence interval (CI). We performed a Trial Sequential Analysis (TSA) assuming an alpha risk of 5%. The primary outcome was the time to first rescue analgesia.
EVIDENCE SYNTHESIS
Eight RCTs were included. Time to first rescue analgesia was significantly longer when the α-2 agonists were used (MD 85.9 min [95% CI: 23.8, 147.9]; P=0.007). Duration of sensory block was also longer in the α-2 group (MD 40.5 [95% CI: 20.21,60.7]; P<0.0001), while no differences were found for onset of sensory block and onset and duration of motor block. Rates of shivering and nausea or vomiting were significantly lower in the α-2 agonist group, while risk of hypotension or respiratory depression were not different. The TSA on the primary outcome suggests the need of further research before drawing conclusions.
CONCLUSIONS
α2-agonists seem to increase the time to first rescue analgesia and to prolong the duration of sensory block when used as adjuvants to LA in CS patients compared to fentanyl. Also, α2-agonists may reduce the incidence of shivering and nausea or vomiting.
Topics: Pregnancy; Female; Humans; Anesthesia, Spinal; Fentanyl; Anesthetics, Local; Pain; Adrenergic alpha-2 Receptor Agonists; Vomiting; Nausea; Adjuvants, Pharmaceutic; Cesarean Section; Adjuvants, Anesthesia
PubMed: 36448990
DOI: 10.23736/S0375-9393.22.16969-5 -
Medicine Nov 2022Meta-analysis was used to evaluate the efficacy of Fufang Biejia Ruangan Tablets in the treatment of chronic hepatitis B (CHB) liver fibrosis. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Meta-analysis was used to evaluate the efficacy of Fufang Biejia Ruangan Tablets in the treatment of chronic hepatitis B (CHB) liver fibrosis.
METHODS
Databases, including PubMed, China Knowledge Network (CNKI), China Biomedical Database (CBM), Wan Fang, VIP database, Embase, and Cochrane Library were searched. The time was searched up to May 2022. The participant intervention comparator outcomes of this study were as follows: P, patients with CHB liver fibrosis; I, Fufang Biejia Ruangan Tablets; C, pharmacological placebo; O, the efficacy rate, alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), albumin (ALB), procollagen III protein (PIIIP), hyaluronic acid (HA), laminin (LN), collagen C type IV (IV-C), portal vein diameter, spleen thickness and HBV-DNA negative conversion rate. The Cochrane Risk of Bias tool, Begg's test and Egger's test were used to evaluate the methodological quality of eligible studies. A randomized controlled trial of Fufang Biejia Ruangan Tablets was used to treat CHB liver fibrosis. Three reviewers independently selected trials, extracted data, cross-checked, and performed methodological quality assessments. Data analysis was completed by Review Manager 5.3.
RESULTS
Twenty-six studies with 2717 patients were included in the meta-analysis. The meta-analysis showed that Fufang Biejia Ruangan Tablets was effective by increasing the efficacy. Fufang Biejia Ruangan Tablets was more efficient in improving ALT, AST, TBIL, ALB, PIIIP, HA, LN, IV-C, portal vein diameter, spleen thickness, and HBV-DNA negative conversion rate with no serious adverse reactions.
CONCLUSION
It was shown that Fufang Biejia Ruangan Tablets can effectively improve liver function and relieve liver fibrosis, but future research should focus on rigorously designed, multicenter, and large randomized controlled trials.
Topics: Humans; Hepatitis B, Chronic; DNA, Viral; Liver Cirrhosis; Alanine Transaminase; Tablets; Adjuvants, Pharmaceutic; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 36401442
DOI: 10.1097/MD.0000000000031664 -
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 -
Pharmacological Research Nov 2022As the worldwide population progresses in age, there is an increasing need for effective treatments for age-associated musculoskeletal conditions such as osteoporosis... (Review)
Review
As the worldwide population progresses in age, there is an increasing need for effective treatments for age-associated musculoskeletal conditions such as osteoporosis and osteoarthritis (OA). Fisetin, a natural flavonoid, has garnered attention as a promising pharmaceutical option for treating or delaying the progression of osteoporosis and OA. However, there is no systematic review of the effects of fisetin on bone and cartilage. The aim of this review is to report the latest evidence on the effects of fisetin on bone and cartilage, with a focus on clinical significance. The PubMed, Embase, and Cochrane Library databases were searched up to December 9th 2021 to evaluate the effects of fisetin on bone and cartilage in in vitro studies and in vivo preclinical animal studies. The risk of bias, quality, study design, sample characteristics, dose and duration of fisetin treatment, and outcomes of the 13 eligible studies were analyzed in this systematic review. Qualitative evaluation was conducted for each study due to differences in animal species, cell type, created disease model, dose and duration of fisetin treatment, and time between intervention and assessment among the eligible studies. The beneficial effects of fisetin on osteoporosis have been demonstrated in in vitro and in vivo preclinical studies across animal species. Similarly, the beneficial effects of fisetin on OA have been demonstrated in in vivo preclinical animal studies, but the reports on OA are still limited. Fisetin, a natural supplement can be use in orthobiologics treatment, as adjuvant to orthopaedic surgery, to improve clinical outcome.
Topics: Animals; Flavonols; Osteoarthritis; Osteoporosis; Cartilage
PubMed: 36243333
DOI: 10.1016/j.phrs.2022.106504