Addressing Patient Safety Hazards Using Critical Incident Reporting in Hospitals: A Systematic Review.

INTRODUCTION: Critical incident reporting systems (CIRS) are in use worldwide. They are designed to improve patient care by detecting and analyzing critical and adverse patient events and by taking corrective actions to prevent reoccurrence. Critical incident reporting systems have recently been criticized for their lack of effectiveness in achieving actual patient safety improvements. However, no overview yet exists of the reported incidents' characteristics, their communication within institutions, or actions taken either to correct them or to prevent their recurrence. Our main goals were to systematically describe the reported CIRS events and to assess the actions taken and their learning effects. In this systematic review of studies based on CIRS data, we analyzed the main types of critical incidents (CIs), the severity of their consequences, their contributing factors, and any reported corrective actions. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we queried MEDLINE, Embase, CINAHL, and Scopus for publications on hospital-based CIRS. We classified the consequences of the incidents according to the National Coordinating Council for Medication Error Reporting and Prevention index, the contributing factors according to the Yorkshire Contributory Factors Framework and the Human Factors Classification Framework, and all corrective actions taken according to an action hierarchy model on intervention strengths. RESULTS: We reviewed 41 studies, which covered 479,483 CI reports from 212 hospitals in 17 countries. The most frequent type of incident was medication related (28.8%); the most frequent contributing factor was labeled "active failure" within health care provision (26.1%). Of all professions, nurses submitted the largest percentage (83.7%) of CI reports. Actions taken to prevent future CIs were described in 15 studies (36.6%). Overall, the analyzed studies varied considerably regarding methodology and focus. CONCLUSIONS: This review of studies from hospital-based CIRS provides an overview of reported CIs' contributing factors, characteristics, and consequences, as well as of the actions taken to prevent their recurrence. Because only 1 in 3 studies reported on corrective actions within the healthcare facilities, more emphasis on such actions and learnings from CIRS is required. However, incomplete or fragmented reporting and communication cycles may additionally limit the potential value of CIRS. To make a CIRS a useful tool for improving patient safety, the focus must be put on its strength of providing new qualitative insights in unknown hazards and also on the development of tools to facilitate nomenclature and management CIRS events, including corrective actions in a more standardized manner.

Noxa/Mcl-1 balance influences the effect of the proteasome inhibitor MG-132 in combination with anticancer agents in pancreatic cancer cell lines.

Pancreatic cancer progresses aggressively and owing to chemoresistance responds poorly to chemotherapy. Thus, there is an urgent need to understand the mechanisms of cancer cell resistance to generate effective strategies to circumvent intrinsic chemoresistance in this tumour indication. In this study, three pancreatic cancer cell lines, MIA PaCa-2, MDAPanc-3 and AsPC-1, were treated with the proteasome inhibitor MG-132 together with camptothecin, doxorubicin or paclitaxel, and cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The combination of MG-132 and camptothecin at a ratio of 5 : 1 gave the most promising results and enhanced cytotoxicity compared with the single compounds in MIA PaCa-2 cells. The increase was shown to be due to enhanced caspase-3 activity resulting in apoptosis. Moreover, this combination upregulated the levels of the proapoptotic protein Noxa and reduced the levels of the antiapoptotic protein Mcl-1, as demonstrated by western blotting. In contrast, the combination of MG-132 with doxorubicin also induced increased cytotoxicity, but apoptosis was decreased. The lack of an enhanced apoptosis induction could be correlated with high levels of Mcl-1 in response to the combined treatment with MG-132 and doxorubicin. Thus, the results indicate that regulation of the antiapoptotic and proapoptotic Bcl-2 family members Noxa and Mcl-1 is predicative of the effectiveness of the combination of MG-132 with different anticancer agents on apoptosis induction in pancreatic cancer cells.

Polymorphism C3435T of the MDR-1 gene predicts response to preoperative chemotherapy in locally advanced breast cancer.

P-glycoprotein, encoded by the MDR-1 gene, confers multi-drug resistance against antineoplastic agents and is important for the transmembrane transition of various other common therapeutic drugs. Recently, a number of polymorphisms in the MDR-1 gene were identified and the T/T genotype at position 3435 in exon 26 was found to correlate with intestinal P-glycoprotein expression and bioavailability of digoxin after oral administration. We analysed the allelic frequencies at the polymorphic site C3435T in a group of patients with locally advanced breast cancer treated by preoperative chemotherapy to evaluate its predictive value. Sixty-eight patients diagnosed between 1998 and 2001 were treated by preoperative chemotherapy with anthracyclines or these agents combined with taxanes. From genomic DNA, a 106 bp fragment of MDR-1 exon 26 was amplified and the C3435T genotype was determined by Pyrosequencing methodology. A potential correlation with therapeutic response was calculated with Fisher's exact test. The overall clinical response rate (cCR and cPR) was 68% but only 7 patients (10.3%) achieved pathological complete response (pCR). Heterozygous C3435T occurred in 57% of the subjects and 22% of the analysed individuals possessed only T alleles. Statistical analysis revealed a significant correlation (p=0.029) between clinical complete response to preoperative chemotherapy and the T/T genotype. MDR-1 polymorphism C3435T in exon 26 may co-determine resistance to chemotherapy and provide useful information to individualize therapy.