Correction: Risk factors for drug-related problems in a general hospital: A large prospective cohort.

[This corrects the article DOI: 10.1371/journal.pone.0230215.].

Analgesic efficacy of lidocaine and multimodal analgesia for chest tube removal: A randomized trial study.

OBJECTIVE: To assess the analgesic efficacy of subcutaneous lidocaine and multimodal analgesia for chest tube removal following heart surgery. METHODS: Sixty volunteers were randomly allocated in two groups; 30 participants in the experimental group were given 1% subcutaneous lidocaine, and 30 controls were given a multimodal analgesia regime comprising systemic anti-inflammatory agents and opioids. The intensity and quality of pain and trait and state anxiety were assessed. The association between independent variables and final outcome was assessed by means of the Chi-squared test with Yates' correction and Fisher's exact test. RESULTS: The groups did not exhibit significant difference with respect to the intensity of pain upon chest tube removal (p= 0.47). The most frequent descriptors of pain reported by the participants were pressing, sharp, pricking, burning and unbearable. CONCLUSION: The present study suggests that the analgesic effect of the subcutaneous administration of 1% lidocaine combined with multimodal analgesia is most efficacious.

Decrease in Fungizone toxicity induced by the use of Lipofundin as a dilutent: an in vitro study.

The aim of this work was to develop an in vitro experimental protocol for the evaluation of toxicity and efficacy of an amphotericin B (AmB) micelle system, Fungizone, which was previously diluted with a lipid based emulsion for parenteral use, named Lipofundin LCT/MCT-20%. Two cell models were used for the experiments: Red Blood Cells (RBC) from human donnors and Candida tropicalis (Ct). These models were used to perform the toxicity and activity of the Fungizone/ Lipofundin admixture (AmB-LP) and the Fungizone (AmB-M) alone. While potassium (K+) and hemoglobin leakage from RBC were the parameters used to evaluate the acute and chronic toxicity, respectively, the efficacy of AmB-LP and AmB-M were assessed by K+ leakage or cell survival rate (CSR) from Ct. The results show that the toxicity of AmB-LP to RBC was concentration dependent concerning the K+ leakage; while at high concentrations, 5 and 50 mg x mL(-1), the leakage was 50.91 +/- 2.09% and 95.71 +/- 0.64%, respectively, at a concentration of 0.5 mg x mL(-1) this value was 17.16 +/- 1.57% and the value tended to zero for the lowest concentration studied, 0.05 mg x mL(-1). Surprisingly, AmB-LP induced very low hemoglobin leakage for all concentrations studied. At the highest concentration, 50 mg x mL(-1), this value was around 3%. When the cell model was Ct, the results changed completely. Not only high concentrations of AmB-LP, but also lower ones were able to induce a K+ permeability of around 100%. The CSR parameter showed an inverse correlation with the concentration; high values, between 50 and 5 mg x mL(-1), resulted in a CSR of around 8%. On the other hand, for lower concentration values, 0.05 and 0.5 mg x mL(-1), this one was around 80%. The same profile of activity against Ct was found for AmB-M. Only a small variation was found for the K+ leakage at 0.05 mg x mL(-1) that presented a value of 96.99 +/- 2.53%. However, AmB-M seemed to be much more toxic than AmB-LP. Its induction of hemoglobin leakage started at 0.5 mg x mL(-1) and reached the 100% at 5 mg x mL(-1). K+ leakage results were worse. The intermediate concentrations of study, 0.5 and 5 mg x mL(-1), presented a significant increase compared to AmB-LP. All together these results reveal that the activity of AmB is not only concentration dependent, but also depends on the drug carrier in which this compound was inserted. The AmB-LP preparation showed the same efficacy as AmB-M, but with a low toxicity. Therefore, AmB-LP presented a higher therapeutic index that permits the administration of high concentration of AmB without revealing side effects. However, the simple mixture of two complex pharmaceutical entities, as micelles and emulsions, should be analyzed carefully to assure that physicochemical stability is not reduced and thereby cause a different biodistribution in vivo.