scholarly journals Do we need still more trials on T4 and T3 combination therapy in hypothyroidism?

2009 ◽  
Vol 161 (6) ◽  
pp. 955-959 ◽  
Author(s):  
Wilmar M Wiersinga
Keyword(s):  
Clinical Trials ◽  
Combination Therapy ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Well Being ◽  
Once Daily ◽  
Serum Free ◽  
Physiological Serum ◽  
Levothyroxine Replacement ◽  
Hypothyroid Patients

Approximately 10% of hypothyroid patients are dissatisfied with the outcome of levothyroxine replacement. It is unlikely that slight over- or under-treatment with thyroxine (T4) explains remaining complaints. Meta-analysis of randomized clinical trials shows no advantage of T4/tri-iodothyronine (T3) combination therapy over T4 monotherapy. However, each of these trials can be criticized, and none is perfect: most of them failed to mimic the physiological ratio of serum free T4 (FT4) to free T3 (FT3) concentrations. Development of a sustained-release T3 preparation given as a single nighttime dose (together with levothyroxine once daily) might maintain physiological serum FT4–FT3 ratio's throughout 24 h. Genetic polymorphisms in deiodinase 2 and thyroid hormone transporters have been associated with well-being, fatigue, depression, and greater improvement on combination therapy. Future trials should target carriers of these polymorphisms to see whether they do better on T4/T3 combination therapy than on T4 monotherapy.

Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A systematic review and meta-analysis of randomized trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14577-e14577
Author(s):  
Domenico Ciliberto ◽  
Cirino Botta ◽  
Pierpaolo Correale ◽  
Roberto Mazzanti ◽  
Giovanni Mantovani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pancreatic Cancer ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Single Agent ◽  
Advanced Pancreatic Cancer ◽  
Final Analysis ◽  
Combination Regimens

e14577 Background: Pancreatic cancer is the 4th leading cause of cancer-related death worldwide. Single-agent chemotherapy with gemcitabine represents a cornerstone for advanced disease treatment. To date, almost all trials, designed to evaluate the benefit of the addition of a second agent to gemcitabine, failed to demonstrate an improvement in overall survival (OS). We performed a systematic review and a meta-analysis of randomized clinical trials to assess the efficacy and safety of gemcitabine-based combination regimens versus gemcitabine alone in the management of pancreatic cancer. Methods: Clinical trials were selected by searching Medline database and abstracts from major cancer meetings. We considered the Jan 1997 - Jan 2012 time frame. Primary end-point was OS, secondary end-points were response rate (RR), disease control rate (DCR) and safety. Hazard ratios (HRs) of OS, odds-ratios (ORs) of RR, DCR and risk ratios of grade 3-4 toxicity rates, were extracted as presented in retrieved studies and used for statistical analysis. Meta-analytic estimates were derived using random-effects model. Results: Thirty-three trials for a total of 10371 patients were selected and included in the final analysis. The analysis showed for combination chemotherapy a benefit in terms of OS (HR: 0.92; 95%CI: 0.88-0.96; p < 0.001). OR of both RR and DCR demonstrated a significant advantage for combination therapy (OR for RR: 0.63, 95%CI: 0.50-0.80, p=0.006; OR for DCR: 0.78; 95%CI: 0.64-0.94; p=0.002). Toxicities were more frequent in the combination treatment group and a significant value in term of risk ratio was reached for diarrhea (0.53, 95%CI: 0.36-0.79), nausea (0.74, 95%CI: 0.56-0.96), neutropenia (0.74, 95%CI: 0.62-0.89) and thrombocytopenia (0.59, 95%CI: 0.44-0.79). Conclusions: Combinationchemotherapy compared to gemcitabine alone significantly improves OS. However, this advantage seems to be marginal and at the cost of increased toxicity, suggesting the use of gemcitabine-based combination regimens only in selected patients. New approaches based on preclinical findings, in the era of targeted therapy, are eagerly awaited on this specific topic.

scholarly journals Effect of Combined Diclofenac and B Vitamins (Thiamine, Pyridoxine, and Cyanocobalamin) for Low Back Pain Management: Systematic Review and Meta-analysis

Pain Medicine ◽  
2019 ◽  
Vol 21 (4) ◽  
pp. 766-781 ◽  
Author(s):  
Carlos-Alberto Calderon-Ospina ◽  
Mauricio Orlando Nava-Mesa ◽  
Carlos Emilio Arbeláez Ariza
Keyword(s):  
Clinical Trials ◽  
Low Back Pain ◽  
Back Pain ◽  
Combination Therapy ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Selective Reporting ◽  
Low Back ◽  
High Quality

Abstract Background Cumulative evidence suggests an analgesic effect of thiamine, pyridoxine, and cyanocobalamin (TPC) in monotherapy, and also when combined with nonsteroidal anti-inflammatory drugs (NSAIDs), particularly diclofenac, in a synergistic manner. The aim of this review was to determine the effects of diclofenac combined with TPC compared with diclofenac monotherapy for low back pain (LBP) management. Methods We searched for randomized clinical trials on the MEDLINE, EMBASE, LILACS, and Cochrane databases of records of clinical trials, among other sources. We evaluated the risk of bias regarding randomization, allocation concealment, blinding, incomplete outcome data, selective reporting, and other biases. A random-effects meta-analysis to examine patients with acute LBP (N = 1,108 adults) was performed, along with a subsequent sensitivity analysis. Results Five studies in patients with LBP were included in the qualitative synthesis. Four of these studies in acute LBP were included in the first meta-analysis. A sensitivity test based on risk of bias (three moderate- to high-quality studies) found that the combination therapy of diclofenac plus TPC was associated with a significant reduction in the duration of treatment (around 50%) compared with diclofenac monotherapy (odds ratio = 2.23, 95% confidence interval = 1.59 to 3.13, P &lt; 0.00001). We found no differences in the safety profile and patient satisfaction. Conclusions This meta-analysis demonstrated that combination therapy of diclofenac with TPC might have an analgesic superiority compared with diclofenac monotherapy in acute LBP. However, there is not enough evidence to recommend this therapy in other types of pain due to the scarcity of high-quality studies.

Maternal and Neonatal Effect of Fentanyl as a Premedication before Induction of General Anesthesia in Cesarean Surgery: A Systematic Review and Meta-analysis of Randomized Clinical Trials

2019 ◽  
Vol 15 (4) ◽  
pp. 232-237
Author(s):  
Mir Hadi Musavi ◽  
Behzad Jodeiri ◽  
Keyvan Mirnia ◽  
Morteza Ghojazadeh ◽  
Zeinab Nikniaz
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Cesarean Section ◽  
General Anesthesia ◽  
Apgar Score ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Intravenous Fentanyl ◽  
Neonatal Effect ◽  
Fentanyl Group

Background: Although, some clinical trials investigated the maternal and neonatal effect of fentanyl as a premedication before induction of general anesthesia in cesarean section, to the best of our knowledge, there is no systematic review to summarize these results. Objectives: The present systematic review and meta-analysis evaluated the maternal and neonatal effect of intravenous fentanyl as a premedication before induction of general anesthesia in cesarean section. Methods: The databases of Pubmed, Embase, Scopus and Cochrane library were searched till July 2017 to identify randomized clinical trials which evaluated the effects of intravenous fentanyl as a premedication before induction of general anesthesia compared with placebo on neonate first and fifth minute Apgar score and maternal heart rate and mean arterial pressure (MAP) in cesarean section. Standard Mean difference (SMD) was calculated and I-square statistic test was used for heterogeneity analysis. Results: The present systematic review and meta-analysis consisted of three clinical trials including 180 women in labor. Considering the results of meta-analysis, there is no significant differences between fentanyl and placebo in the case of Apgar score at 1 minute; however, the Apgar score of 5 minutes was significantly lower in fentanyl group compared with placebo (SMD -0.68, 95%CI: - 0.98, -0.38, p<0.001). In the term of maternal hemodynamics, the heart rate (SMD -0.43, 95%CI: - 0.72, -0.13, p=0.004) and MAP (SMD -0.78, 95% CI: -1.09, -0.48, p<0.001) in fentanyl group were significantly lower compared with placebo group. Conclusion: The present meta-analysis showed that using intravenous fentanyl as a premedication before induction of general anesthesia had adverse effects on neonate Apgar score. However, it had positive effects on preventing adverse consequences of intubation on maternal hemodynamics.

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