Inhibition of CXCR2 Plays a Pivotal Role in Re-Sensitizing Ovarian Cancer to Cisplatin Treatment

cDNA microarray data conducted by our group revealed overexpression of CXCL2 and CXCL8 in ovarian cancer (OC) microenvironment. Herein, we have proven that the chemokine receptor, CXCR2, is a pivotal molecule in re-sensitizing OC to cisplatin, and its inhibition decreases cell proliferation, viability, tumor size in cisplatinresistant cells, as well as reversed the overexpression of mesenchymal epithelium transition markers. Altogether, our study indicates a central effect of CXCR2 in preventing tumor progression, due to acquisition of cisplatin chemoresistant phenotype by tumor cells, and patients’ high lethality rate. We found that the overexpression of CXCR2 by OC cells is persistent and anomalously confined to the cellular nuclei, thus pointing to an urge in developing highly lipophilic molecules that promptly permeate cells, bind to and inhibit nuclear CXCR2 to fight OC, instead of relying on the high-cost genetic engineered cells.acknowledge financial support from CAPES, FAPES and CNPq, as well as the Biotechnology Program/ RENORBIO from the Federal University of Espirito Santo, Espirito Santo, Brazil; Institute of Pathology and Molecular Immunology (IPATIMUP) and the Institute of Innovation and Health Research (I3s), Porto, Portugal

Medication dispensing as an opportunity for patient counseling and approach to drug-related problems

ABSTRACT The objective was to describe and evaluate a model of drug dispensing developed and implemented in a community pharmacy in Brazil. This was a descriptive, observational, quasi-experimental study performed in the period between 21 January 2013 and 20 April 2013. The model was evaluated and described in terms of three parameters: structure, process and outcome. The description and assessment of each parameter was performed as follows: (I) Structure: profile of patients, pharmacist's professional profile, physical facility, informational material; (II) Process: drug-related problems, pharmaceutical interventions performed, results of pharmaceutical interventions; (III) Outcome: patient knowledge of medications. Dispensing service improved patient knowledge of medications (p < 0.05), which was associated with pharmacotherapy complexity (p < 0.05). The main problems identified were related to lack of patient knowledge regarding their medication (52.9%). Pharmaceutical interventions were mostly performed directly to the patients (86.3%) by verbal (95.4%) and written (68.2%) information, and most of the problems were completely solved (62.7%). The medicine dispensing model was able to identify and solve drug-related problems and promote an improvement in patient knowledge about medication

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin.This study was sponsored by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Support for third-party writing assistance for this manuscript, furnished by Blair Jarvis MSc, ELS, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin

Electronic prescription as contributing factor for hospitalized patients' safety.

The following study was performed to identify factors related to medication errors in the computerized physician order entry and their advantages and disadvantages according to doctors, nursing team and administrative officers. It is a survey descriptive study carried out at three units of a Brazilian academic hospital in the southeast area. The study was divided in two phases. In the first phase, we analyzed a total of 1,349 prescriptions from general medical unit, surgical and orthopaedic wards during 30 days consecutively. A semi-structured instrument, elaborated by a group of researchers for the study proposals, was used. In the second phase, a semi-structured questionnaire was applied to the health professionals containing closed and open items approaching their opinion about the composition of electronic prescription, the advantages and disadvantages of them, and their suggestions for its improvement. Out of 1,349 prescriptions observed, 17.5% presented deletions, 25.0% medicines written manually and 17.0% of them were incomplete. Some of the advantages pointed by health professionals were its legibility (37.5%), little time spent when elaborating and emitting them (20.5%) and the way they are a practical and organized (8%). The disadvantages pointed were repetition of previous prescriptions (34%), typing mistakes (17%), dependence on computers (11%) and alterations made manually (7%). We conclude, this way, that the computerized prescription order entry represents a great progress among the strategies used to minimize medication errors caused by prescriptions badly formulated. However, it doesn't eradicate the possibility of medication error occurrences, needing some system modifications

Biological nitrogen fixation in field-grown sorghum under different edaphoclimatic conditions is confirmed by N isotopic signatures.

The association between sorghum and N2-fixing bacteria has been assessed only under limited conditions. We investigated biological nitrogen fixation (BNF) in situ in fifteen sorghum genotypes with dry or succulent culm types under five edaphoclimatic conditions. One randomized block experiment was established in each of five locations, from the humid to the semiarid regions of Pernambuco state, Brazil. BNF was estimated using the 15N natural abundance method by comparing the average d15N value of each sorghum genotype with those of the reference species. High levels of productivity, up to 22 Mg shoot biomass ha-1 in the 3-month cycle, were obtained where rainfall was high, and up to 5 Mg ha-1 was obtained under low rainfall. The nitrogen contents showed a similar pattern as biomass production, and the genotypes with the highest productivity accumulated from 200 to 300 kg N ha-1. BNF ranged from 55 to 78% of plant N in one location and from 36 to 56% in another location, but BNF did not occur in the other three locations. Although the factors that blocked effective symbiosis were not determined, symbiosis was not influenced by P or K availability. The proportion of N2 fixation was similar in the grainproducing, dry culm genotypes and in the sugar-rich, succulent culm genotypes. The sorghum genotypes fixed N2, reaching up to 218 kg ha-1 N, without inoculation with diazotrophs. Therefore, sorghum has a high potential to fix atmospheric N2, but the factors that block N2 fixation must be identified for crop management planning