scholarly journals Dosing and safety of cyclosporine in patients with severe brain injury

2008 ◽  
Vol 109 (4) ◽  
pp. 699-707 ◽  
Author(s):  
Jimmi Hatton ◽  
Bonnie Rosbolt ◽  
Philip Empey ◽  
Richard Kryscio ◽  
Byron Young
Keyword(s):  
Placebo Group ◽  
Brain Injury ◽  
Adverse Events ◽  
Placebo Treatment ◽  
Blood Concentrations ◽  
Significant Difference ◽  
Immunological Effects ◽  
Male Patients ◽  
Injury Models ◽  
Score Range

Object Cyclosporine neuroprotection has been reported in brain injury models but safety and dosing guidelines have not been determined in humans with severe traumatic brain injury (TBI). The purpose of this investigation was to establish the safety of cyclosporine using 4 clinically relevant dosing schemes. Methods The authors performed a prospective, blinded, placebo-controlled, randomized, dose-escalation trial of cyclosporine administration initiated within 8 hours of TBI (Glasgow Coma Scale score range 4–8; motor score range 2–5). Four dosing cohorts (8 patients treated with cyclosporine and 2 receiving placebo treatment per cohort) received cyclosporine (1.25–5 mg/kg/day) or placebo in 2 divided doses (Cohorts I–III) or continuous infusion (Cohort IV) over 72 hours. Adverse events and outcome were monitored for 6 months. Results Forty patients were enrolled over 3 years (cyclosporine cohorts, 24 male and 8 female patients; placebo group, 8 male patients). Systemic trough concentrations were below 250 ng/ml during intermittent doses. Higher blood concentrations were observed in Cohorts III and IV. There was no significant difference in immunological effects, adverse events, infection, renal dysfunction, or seizures. Mortality rate was not affected by cyclosporine administration, independent of dose, compared with placebo (6 of 32 patients receiving cyclosporine and 2 of 8 receiving placebo died, p > 0.05). At 6 months, a dose-related improvement in favorable outcome was observed in cyclosporine-treated patients (p < 0.05). Conclusions In patients with acute TBI who received cyclosporine at doses up to 5 mg/kg/day, administered intravenously, with treatment initiated within 8 hours of injury, the rate of mortality or other adverse events was not significantly different from that of the placebo group.

scholarly journals Efficacy and safety of sprifermin injection for knee osteoarthritis treatment: a meta-analysis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Ni Zeng ◽  
Xin-Yuan Chen ◽  
Zhi-Peng Yan ◽  
Jie-Ting Li ◽  
Tao Liao ◽  
...  
Keyword(s):  
Adverse Events ◽  
Knee Osteoarthritis ◽  
Meta Analysis ◽  
Placebo Treatment ◽  
Cartilage Volume ◽  
Cartilage Thickness ◽  
Random Effects Models ◽  
Structural Progression ◽  
Significant Difference ◽  
Mean Differences

Abstract Objective To perform a meta-analysis comparing the structural progression and clinical symptom outcomes as well as adverse events experienced from intra-articular injections of sprifermin compared to a placebo treatment for patients with knee osteoarthritis (KOA). Method We systematically searched the literature for studies that compared long-term outcomes between sprifermin and placebo injections for KOA treatment. Meta-analysis was performed with RevMan5.3 using an inverse variance approach with fixed or random effects models. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Results Eight studies were included. Overall, there was significantly less improvement of WOMAC total scores in patients receiving sprifermin, compared with the placebo (mean difference (MD) = 3.23, 95% CI 0.76–5.69; I2 = 0%; P = 0.01). Further, sprifermin injection patients gained more, and lost less, cartilage thickness and volume in total femorotibial joint (cartilage thickness: standardized mean differences (SMD) = 0.55, 95% CI 0.26–0.84; I2 = 78%; P = 0.0002; cartilage volume: SMD = 0.39, 95% CI 0.20–0.58; I2 = 49%; P < 0.0001). Changes in the cartilage surface morphology of the medial tibio-femoral joint (MD = −0.30, 95% CI −0.44 to −0.16; I2 = 0%; P < 0.0001) and patello-femoral joint (MD = −0.22; 95% CI −0.37 to −0.07; I2 = 0%; P = 0.004) showed a significant difference between the sprifermin and placebo injections. Moreover, there were no significant differences between sprifermin and the placebo in the risk of treatment-emergent adverse events (OR = 1.05; 95% CI 0.52–2.14; I2 = 48%; P = 0.89). Conclusion The data from the included studies provide strong evidence to determine the effect of intra-articular sprifermin on joint structure in individuals with KOA and show no specific adverse effects. Nevertheless, intra-articular sprifermin did not likely have any positive effect on symptom alleviation.

scholarly journals COMPARISON OF EFFICACY AND SAFETY SILODOSIN 8 MG ONCE DAILY AND SILODOSIN 4 MG TWICE DAILY IN BPH PATIENTS WITH LUTS

2019 ◽  
Vol 26 (1) ◽  
Author(s):  
Ramzie Nendra Diansyah ◽  
Johan Renaldo ◽  
Wahjoe Djatisoesanto ◽  
Lukman Hakim
Keyword(s):  
Adverse Events ◽  
Side Effect ◽  
Similar Efficacy ◽  
Common Adverse Event ◽  
Common Side Effect ◽  
Urinary Flow ◽  
Once Daily ◽  
Significant Difference ◽  
Male Patients ◽  
Maximum Urinary Flow

Objective: This study was aimed to compare the efficacy and side effect of silodosin 8mg once daily and silodosin 4mg twice daily in BPH-LUTS patients after 4 and 12 weeks. Material & Methods: Single blind randomized controlled trials in 60 male patients aged ≥45 years with BPH-LUTS from July 2017 to October 2017 was divided into groups who received 8mg of silodosin once daily and those who received 4mg of silodosin twice daily. Efficacy and adverse events were evaluated after 4 and 12 weeks of treatment. Results:  There was no significant difference of mean age of the two groups was 67.93 ± 6.49 years and 69.07 ± 6.28 years respectively (p 0.49). Both doses of this drug decreased the International Prostate Symptom Score (IPSS) and significantly increased the maximum urinary flow (Qmax) (p<0.05) but there was no significant differences between the two groups (p>0.05). Ejaculation disorder was the most common side effect in all groups (6.7% and 5%) and there was no significant difference between the two groups (p>0.05). Conclusion: The administration of 8mg of once daily silodosin has similar efficacy as 4mg twice daily silodosin. There were no adverse events differences in the two groups. Ejaculation disorder is the most common adverse event of silodosin administration.

Efficacy and Safety of PEGPH20 in Pancreatic Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 17 ◽  
Author(s):  
Vinod Solipuram ◽  
Harish Gopalakrishna ◽  
Gayatri Naira ◽  
Akhila Mohan
Keyword(s):  
Pancreatic Cancer ◽  
Placebo Group ◽  
Febrile Neutropenia ◽  
Adverse Events ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Thromboembolic Events ◽  
Serious Adverse Events ◽  
Significant Difference

Introduction: Pancreatic cancer is an aggressive tumor that had an estimated 57,600 new cases and 47,050 deaths in 2020 in the US alone. Recent studies have targeted tumor microenvironment (TME) for better delivery of systemic chemotherapy like PEGPH20, which degrades hyaluronic acid in the extracellular matrix (ECM). A meta-analysis of these Randomized controlled trials (RCTs) to test the efficacy of PEGPH20 was performed. Methods: A systematic search was performed using PubMed, Embase, and Cochrane library without language limitations from inception to July 30, 2020. A total of 59 articles was identified, and 3 RCTs were included in the final analysis. The primary outcome was progression-free survival (PFS), and secondary outcomes were overall survival (OS), deaths from adverse events, thromboembolic events, serious adverse events (SAE), and febrile neutropenia. Results: There was no statistically significant improvement in PFS (HR= 0.94; 95%CI (0.79, 1.11)) in the PEGPH20 group when compared to the standard treatment/placebo group. There was no significant difference among OS (HR= 0.99, 95%CI (0.83, 1.17), deaths from adverse events (RR=0.97; 95%CI (0.54, 1.73)), thromboembolic events (RR= 1.49; 95%CI (0.92, 2.44)), and febrile neutropenia (RR= 0.88; 95%CI (0.45, 1.72), however, there was statistically significant increase in SAE (RR = 1.59; 95%CI (1.01, 2.52) in the PEGPH20 group compared to the placebo group. Conclusion: This meta-analysis showed that PEGPH20 did not improve the PFS or OS. Moreover, there is an increased incidence of serious adverse events with the use of PEGPH20 compared to standard therapies.

A randomized, double-blinded clinical trial of royal jelly intake for anticancer effects and suppressing adverse events in renal cell carcinoma patients treated with tyrosine kinase inhibitors.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 697-697
Author(s):  
Yasuyoshi Miyata ◽  
Kojiro Ohba ◽  
Tomohiro Matsuo ◽  
Kensuke Mitsunari ◽  
Hideki Sakai
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Placebo Group ◽  
Adverse Events ◽  
Renal Cell ◽  
Royal Jelly ◽  
Kinase Inhibitors ◽  
Significant Difference ◽  
Anti Cancer ◽  
Double Blinded

697 Background: Royal jelly (RJ) is a honey bee product secreted from the mandibular glands and hypopharyngeal glands of worker honeybees. RJ has anti-allergy, anti-inflammatory, and immunomodulatory effects. RJ has been reported to improve the anti-cancer effects and suppress the adverse effects of chemotherapeutic agents. The main aim is to clarify the clinical effects of oral intake of RJ in renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKIs). Methods: A randomized, controlled, double-blinded clinical trial with reduction of tumor size and frequencies of adverse events as endpoints was performed in 33 RCC patients who received TKIs in Nagasaki University Hospital. Patients were divided into RJ (n = 16) and placebo (n = 17) groups, and there was no significant difference in all clinical and pathological parameters between the two groups. RJ and placebo were orally administered for 3 months. Results: In this study, 21, 8, and 3 patients were treated with sunitinib, pazopanib, and axitinib, respectively; only 1 patient was treated with sorafenib. Frequencies and severities of fatigue and anorexia in the RJ group was significantly lower than those in the placebo group ( P = 0.003 and 0.015, respectively). Such significant differences between the 2 groups were detected in patients treated with sunitinib, but not in those treated with other TKIs. The number of patients who were given an initial dose of TKIs in the RJ and placebo groups were 7 (43.8%) and 2 (11.8%), respectively, and the relative dose intensity (RDI) of the RJ group (88.6%) was significantly higher ( P = 0.016) than that in the placebo group (68.6%). Regarding anti-cancer effects, the frequency of partial response in the RJ group (n = 5; 41.7%) was higher than that in the placebo group (2; 18.2%); however, such difference was not significant ( P = 0.056). Conclusions: RJ intake can increase RDI. Although a significant difference was not observed, RJ intake observed a trend for improving anti-cancer effects by increasing RDI and maintaining quality of life.

scholarly journals Efficacy of Naldemedine for the Treatment of Opioid-Induced Constipation: A Meta-Analysis

2019 ◽  
Vol 28 (1) ◽  
pp. 41-46 ◽  
Author(s):  
Mohammad Esmadi ◽  
Dina Ahmad ◽  
Alexander Hewlett
Keyword(s):  
Placebo Group ◽  
Adverse Events ◽  
English Language ◽  
Meta Analysis ◽  
Group Versus ◽  
Opioid Therapy ◽  
Period Change ◽  
Common Side Effect ◽  
Spontaneous Bowel Movement ◽  
Significant Difference

Background & Aim: Opioid induced constipation (OIC) is the most common side effect of opioid therapy. It can lead to a decreased quality of life. Naldemedine is a peripherally acting μ-opioid receptor antagonist that has been recently studied in randomized controlled trials (RCTs) for the management of OIC. The aim of this study is to perform a meta-analysis of existing clinical trials to estimate the efficacy and safety of naldemedine in opioid-induced constipation.Methods: A systematic search of PubMed, CINAHL, Scopus, Cochrane database of systematic reviews, and ClinicalTrials.gov registry was performed in March 2018. Two independent reviewers systematically identified prospective RCTs published in the English language that compared the effect of oral naldemedine versus placebo in adults with OIC. Meta-analysis was performed using a random effects model to assess the primary outcome: spontaneous bowel movement (SBM) responder rates. Assessed secondary outcomes were: a change in SBM frequency per week from baseline during the treatment period, change from baseline in the frequency of complete SBM and incidence of treatment-emergent adverse events. Review Manager 5.3 software program was utilized for statistical analysis.Results: Six RCTs met the inclusion criteria. A total of 2,762 patients were included in the meta-analysis. The proportion of SBM responders was significantly higher in the naldemedine group compared to the placebo group (56.4%, vs. 34.7%, p<0.00001). There was no statistically significant difference in treatment-emergent adverse events between naldemedine group and placebo group (mean odds ratio=1.18, p = 0.25, 95% CI: 0.89-1.55). Change in SBM frequency was higher in the naldemedine group versus placebo group (p<0.00001), as well as the change in complete SBM frequency.Conclusions: Naldemedine 0.2 mg daily significantly improved symptoms in patients with opioid-induced constipation and was generally well tolerated. These results support the use of naldemedine for the treatment of opioid-induced constipation.

scholarly journals Efficacy and safety of Kami-guibi-tang for mild cognitive impairment: a pilot, randomized, double-blind, placebo-controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hee-Yeon Shin ◽  
Ha-Ri Kim ◽  
Geon-Ho Jahng ◽  
Chul Jin ◽  
Seungwon Kwon ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Placebo Group ◽  
Mild Cognitive Impairment ◽  
Adverse Events ◽  
Vital Signs ◽  
Efficacy And Safety ◽  
Mri Findings ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Significant Difference

Abstract Background Mild cognitive impairment (MCI) is considered an intermediate phase between normal aging and dementia. As the majority of cases of amnestic MCI (aMCI) progress to Alzheimer’s disease (AD), it is considered the prodromal stage of AD, and a treatment target for prevention of further cognitive decline. However, no medications have been shown to have symptomatic or preventive benefits in MCI. Kami-guibi-tang (KGT) is a traditional herbal formula used in Korean medicine to treat amnesia, which is reported to increase acetylcholine levels via activation of choline acetyltransferase. The objective of this study was to evaluate the efficacy and safety of KGT in patients with aMCI. Methods This study was designed as a single-center, randomized, double-blind, placebo-controlled pilot study. Participants diagnosed with aMCI were randomized to receive either KGT or placebo granules for 24 weeks. The efficacy measure was a change in the Seoul Neuropsychological Screening Battery (SNSB) score. The safety measures included the occurrence of adverse events and abnormalities in vital signs and blood chemistry, electrocardiogram (ECG), and brain magnetic resonance imaging (MRI) findings. Results A total of 16 patients in the KGT group and 14 patients in the placebo group were investigated in the study. The mean score of Clinical Dementia Rating-Sum of Boxes (CDR-SB) significantly improved from 1.53 (0.64) points to 1.13 (0.62) points in the KGT group (p = 0.010), whereas it worsened from 1.61 (0.88) points to 1.75 (0.94) points in the placebo group. There was a significant difference in the CDR-SB scores between the two groups after the intervention (p = 0.045). The total SNSB-D scores and the scores in the memory domain after the treatment were significantly higher than the baseline values in the KGT group, but not in the placebo group. The frequency of adverse events was not significantly different between the two groups, and there were no abnormalities in vital signs or blood test, ECG, and brain MRI findings after the intervention. Conclusions KGT may provide a safe and effective treatment option for patients with aMCI. Further studies with a larger sample size are needed to validate the findings. Trial registration Korean Clinical Trial Registry, ID: KCT0002407; Registered on March 30, 2017, http://cris.nih.go.kr/

scholarly journals Escitalopram add-on in stable Schizophrenia with subsyndromal depression

2020 ◽  
Vol 7 (2) ◽  
pp. 211
Author(s):  
Anil Nischal ◽  
Pooja Singh ◽  
Manu Agarwal ◽  
Anuradha Nischal ◽  
Bandna Gupta ◽  
...  
Keyword(s):  
Mental Illness ◽  
Placebo Group ◽  
Depressive Symptoms ◽  
Adverse Events ◽  
Controlled Trial ◽  
Significant Proportion ◽  
Anti Psychotic ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Significant Difference

Background: Significant proportion of the patients of schizophrenia suffer from subsyndromal symptomatic depressive symptoms (SSD) which not only add to the burden of disease but also to the already pre-existing challenges of living with this serious mental illness. Many psychiatrists prescribe antidepressants to patients with schizophrenia who have subsyndromal symptomatic depressive symptoms but data regarding SSD in schizophrenia is meagre. Aim was to study the effect of addition of Escitalopram on psychopathology, cognition and functioning in patients with stable schizophrenia having subsyndromal depressive symptoms and to compare these parameters with patients treated with antipsychotics alone.Methods: The study was a prospective, 8-week randomized double-blind placebo-controlled trial. Seventy four patients who fulfilled the diagnostic criteria of Schizophrenia on the basis of the ICD10-DCR, adjudged to be stable clinically and not requiring any increase in dose of antipsychotic medication over the last eight weeks were recruited into the study. The patients randomly received either Antipsychotics with add-on Escitalopram (10 mg/day) or Antipsychotics with placebo for 8 weeks. The patients were assessed using the HAM-D, CDRS, PANSS, SCoRS, SOFAS and CGI scores at the end of 8 weeks. Patients were also assessed for adverse events at baseline, week 4 and week 8.Results: A total of sixty-six patients who completed the study were analyzed. The HAM-D, CDRS and PANSS score  showed significantly better cognition and functioning in the patients of add-on Escitalopram group when compared with the placebo group. There was no significant difference between the two groups in terms of observed side effects.Conclusions: Escitalopram addition to the standard anti-psychotic treatment of schizophrenia, in patients having subsyndromal depressive symptoms, results in better cognition and improved functioning.

scholarly journals Antipsychotic Monotherapy for Major Depressive Disorder: A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Akira Nishi ◽  
Kyosuke Sawada ◽  
Hiroyuki Uchida ◽  
Masaru Mimura ◽  
Hiroyoshi Takeuchi
Keyword(s):  
Major Depressive Disorder ◽  
Placebo Group ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Meta Analysis ◽  
Depression Severity ◽  
Major Depressive ◽  
Increased Risk ◽  
Significant Difference

Abstract No clinical guidelines currently recommend antipsychotic monotherapy (APM) for major depressive disorder (MDD). Although several randomized controlled trials (RCTs) have compared the effectiveness, efficacy, and safety of APM versus placebo in patients with MDD, no meta-analysis has examined this topic. We conducted a systematic literature search using MEDLINE and Embase to identify relevant RCTs and performed a meta-analysis to compare the following outcomes between APM and placebo: study discontinuation due to all causes, lack of efficacy, and adverse events, changes in total scores on depression severity scales (e.g., Hamilton Depression Rating Scale and Montgomery Åsberg Depression Rating Scale) and in the Clinical Global Impression - Severity scale (CGI-S) score, and individual adverse event rates. A total of 13 identified studies with 14 comparisons involving 3,197 participants that met the eligibility criteria were included in the meta-analysis. No significant difference was found in study discontinuation due to all causes between the APM and placebo groups. However, there were significant differences in study discontinuation due to lack of efficacy in favor of the APM group and study discontinuation due to adverse events in favor of the placebo group. Compared with the placebo group, the APM group was significantly superior in relation to score reduction on the depression severity scales and CGI-S and inferior in relation to 8 of 23 individual adverse events. APM could be a useful treatment option for the acute phase of MDD, although clinicians should be aware of an increased risk of some adverse events.

Efficacy and Safety of Non-Steroidal Anti-Androgens in Patients with Metastatic Prostate Cancer: Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 15 (1) ◽  
pp. 34-47 ◽  
Author(s):  
Muhammed Rashid ◽  
Madhan Ramesh ◽  
K. Shamshavali ◽  
Amit Dang ◽  
Himanshu Patel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Quality Assessment ◽  
Cochrane Library ◽  
Control Group ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Randomized Controlled ◽  
Significant Difference

Background: Prostate cancer (PCa) is the sixth primary cause of cancer death. However, conflicts are present about the efficacy and safety of Non-steroidal anti-androgens (NSAA) for its treatment. The aim of this study was to assess the efficacy and safety of NSAAs versus any comparator for the treatment of advanced or metastatic PCa (mPCa). Methodology: MEDLINE and the Cochrane Library were searched. References of included studies and clinicaltrials.gov were also searched for relevant studies. Only English language studies after 1990 were considered for review. Randomized controlled trials (RCTs) examining the efficacy and safety of NSAAs as compared with any other comparator including surgery or chemotherapy in mPCa patients were included. The outcomes include efficacy, safety and the tolerability of the treatment. The Cochrane Risk of Bias Assessment Tool was used for quality assessment. Two authors were independently involved in the selection, extraction and quality assessment of included studies and disagreements were resolved by discussion or by consulting a third reviewer. Results: Fifty-eight out of 1307 non-duplicate RCTs with 29154 patients were considered for the review. NSAA showed significantly better progression-free survival [PFS] (Hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.78; P=0.0001), time to distant metastasis or death [TTD] (HR, 0.80; 95% CI 0.73-0.91; p<0.0001), objective response (Odds ratio [OR], 1.64; 95% CI 1.06-2.54; P=0.03) and clinical benefits (OR, 1.33; 95% CI 1.08-1.63; P=0.006) as compared to the control group. There was no significant difference observed between the groups in terms of overall survival (HR, 0.95; 95%CI, 0.87-1.03; P=0.18) and time to progression (HR, 0.93; 95% CI 0.77-1.11; P=0.43). Treatment-related adverse events were more with the NSAA group, but the discontinuation due to lack of efficacy reason was 43% significantly lesser than the control group in patients with mPCa. Rest of the outcomes were appeared to be non-significant. Conclusion: Treatment with NSAA was appeared to be better efficacious with respect to PFS, TTD, and response rate with considerable adverse events when compared to the control group in patients with metastatic PCa.

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