Patient*innen-Sicherheit 4.0: „Fehler der Woche“ – Um die Vorbildfunktion geht’s!

BACKGROUND The rate of mistakes and near misses in clinical medicine remains staggering. The tendency to cover up mistakes is rampant in "name-blame-shame" cultures. The need for safe forums where mistakes can be openly discussed in the interest of patient safety is evident. Following a comprehensive review of the literature, a semi-structured weekly conference, named "mistake of the week" (MOTW), was introduced, enabling physicians to voluntarily discuss their mistakes and near-misses. The MOTW is intended to encourage cultural change in how physicians approach, process, accept and learn from their own and their peers' mistakes. This study seeks to assess if physicians appreciate, benefit from and are motivated to participate in MOTW. METHODS Physicians and medical students of the I. and II. Medizinische Klinik at the Academic Teaching Hospital Klinikum Konstanz (Germany) were eligible to participate voluntarily. Four groups of physicians (n=3-6) and one group of medical students (n=5) volunteered to participate in focus group interviews, which were videotaped, transcribed and analyzed. RESULTS The following success factors are crucial for dealing with and voluntarily disclosing mistakes and near-misses: 1. Exemplification ("follow the boss's lead"), 2. Fixed time slots and a clear forum, 3. Reporting mistakes without fear of penalty or punishment, 4. A trusting working atmosphere. The key effects of the MOTW approach are: 1. People report their mistakes more, 2. Relief, 3. Psychological safety, 4. Lessons learned/errors (potentially) reduced. DISCUSSION The MOTW conference models an ideal forum to mitigate hierarchy and promote a sustainable organizational dynamic in which mistakes and near misses can be discussed in an environment free from "name-blame-shame", with the ultimate goal of potentially improving patient care and safety.Hintergrund (Beinahe-)Fehler kommen im komplexen Gesundheitswesen häufig vor. Hierarchisch geprägte Strukturen begünstigen eine Fehlerkultur des „Name – Blame – Shame“ (benenne, klage an, beschäme), (Beinahe-)Fehler werden vertuscht, verharmlost oder totgeschwiegen. Eine der größten Herausforderungen der modernen Medizin ist die Schaffung eines Umfelds, welches durch offene Berichterstattung (Beinahe-)Fehler systematisch analysiert und ermöglicht, daraus etwas zu lernen. Ärzt*innen haben hierbei wegen des ausgeprägten Hierarchiegefüges und des traditionellen Rollenverständnisses eine Schlüsselfunktion. Methoden Nach entsprechender Literaturanalyse wurde das flächendeckend anzuwendende Modell „Fehler der Woche“ (FdW) entwickelt, welches jedem (ärztlichen) Teammitglied erlaubt, offen über (Beinahe-)Fehler zu berichten. Fünf Fokusgruppen wurden durchgeführt und gemäß qualitativem Forschungsansatz via thematischer Analyse ausgewertet. Ergebnisse Folgende wesentliche Erfolgsfaktoren für einen angstfreien Umgang mit (Beinahe-)Fehlern (Modell FdW) wurden identifiziert: 1. Vorbildfunktion („Der Chef macht’s vor“), 2. fester Zeitslot/„Fehlerbühne“, 3. sanktionsfreies Berichten eigener Fehler, 4. vertrauensvolles Arbeitsklima. Folgende relevanten Auswirkungen resultierten hieraus: 1. eigene Fehler werden häufiger berichtet, 2. Erleichterung/Entlastung, 3. psychologische Sicherheit, 4. Lerneffekt. Diskussion Das Modell „Fehler der Woche“ ist in der Lage, einen nachhaltigen Kulturwandel einzuleiten, gemäß dem Motto „ich bin gewiss nicht stolz darauf, dass mir ein (Beinahe-)Fehler unterlaufen ist – jedoch sehr stolz darauf, dass ich im Sinne der Patient*innen-Sicherheit darüber reden kann“

Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease

Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction

BACKGROUND: Hepatocelluar carcinoma (HCC) is one of the most common cancers worldwide and a major cause of cancer-related mortality. HCC is highly resistant to currently available chemotherapeutic drugs. Defects in apoptosis signaling contribute to this resistance. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 protein family which interferes with mitochondrial activation. In a previous study we have shown that Mcl-1 is highly expressed in tissues of human HCC. In this study, we manipulated expression of the Mcl-1 protein in HCC cells by RNA interference and analyzed its impact on apoptosis sensitivity of HCC cells in vitro. METHODS: RNA interference was performed by transfecting siRNA to specifically knock down Mcl-1 expression in HCC cells. Mcl-1 expression was measured by quantitative real-time PCR and Western blot. Induction of apoptosis and caspase activity after treatment with chemotherapeutic drugs and different targeted therapies were measured by flow cytometry and fluorometric analysis, respectively. RESULTS: Here we demonstrate that Mcl-1 expressing HCC cell lines show low sensitivity towards treatment with a panel of chemotherapeutic drugs. However, treatment with the anthracycline derivative epirubicin resulted in comparatively high apoptosis rates in HCC cells. Inhibition of the kinase PI3K significantly increased apoptosis induction by chemotherapy. RNA interference efficiently downregulated Mcl-1 expression in HCC cells. Mcl-1 downregulation sensitized HCC cells to different chemotherapeutic agents. Sensitization was accompanied by profound activation of caspase-3 and -9. In addition, Mcl-1 downregulation also increased apoptosis rates after treatment with PI3K inhibitors and, to a lower extent, after treatment with mTOR, Raf I and VEGF/PDGF kinase inhibitors. TRAIL-induced apoptosis did not markedly respond to Mcl-1 knockdown. Additionally, knockdown of Mcl-1 efficiently enhanced apoptosis sensitivity towards combined treatment modalities: Mcl-1 knockdown significantly augmented apoptosis sensitivity of HCC cells towards chemotherapy combined with PI3K inhibition. CONCLUSION: Our data suggest that specific downregulation of Mcl-1 by RNA interference is a promising approach to sensitize HCC cells towards chemotherapy and molecularly targeted therapies

Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance

<p>Abstract</p> <p>Background</p> <p>Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>OCT1 (<it>SLC22A1</it>) and OCT3 (<it>SLC22A3</it>) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.</p> <p>Results</p> <p>Real time PCR showed a downregulation of <it>SLC22A1 </it>and <it>SLC22A3 </it>in HCC compared to TST (p ≤ 0.001). A low <it>SLC22A1 </it>expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, <it>SLC22A1 </it>was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low <it>SLC22A1 </it>expression (< median) showed a higher <it>SLC22A3 </it>expression compared to HCC with high <it>SLC22A1 </it>expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the <it>SLC22A3 </it>expression.</p> <p>In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.</p> <p>Conclusion</p> <p>The downregulation of OCT1 is associated with tumor progression and a worse patient survival.</p

Managing hepatitis C in liver transplant patients with recurrent infection

Tim Zimmermann1, Gerd Otto2, Marcus Schuchmann11Department of Internal Medicine, 2Transplantation Surgery, University of Mainz, GermanyAbstract: Hepatitis C virus (HCV) reinfection after liver transplantation (LT) and recurrent hepatitis C often lead to recurrent cirrhosis (RC). RC is one of the most frequent complications resulting in organ failure and early death after LT in HCV-positive patients with reported 5-year rates from 20% to 40%. As HCV-cirrhosis is one of the leading indications for LT, the therapeutic management is a central issue. To date, the best available therapy is a combination of pegylated interferon + ribavirin in patients with established recurrent hepatitis C proven by liver biopsy. Although increasing experience in using interferon therapy after LT has suggested better response rates, treatment is limited by a poor tolerability and high rates of severe side effects, necessitating lower doses or withdrawal of therapy. The extent to which dose reductions and the concomitant administration of growth factors affect virological response or prevent complications is still to be determined. Prospective clinical trials are mandatory to identify the best time point and schedule of antiviral treatment in transplant patients. Currently, therapeutic options need to be discussed for each individual patient. Therefore therapy should be carried out only in transplant centers with experience in managing hepatitis C after LT.Keywords: hepatitis C, liver transplantation, recurrent infection, treatmen

Quality of life as a therapeutic objective in the management of hepatic encephalopathy and the potential role of rifaximin-α

OBJECTIVE: Quality of life (QoL) is impaired in patients with hepatic encephalopathy and rifaximin-α can improve QoL within 6 months. This study assessed the importance of QoL as a therapeutic objective in hepatic encephalopathy management; whether QoL is routinely assessed in hepatic encephalopathy patients in clinical practice and the role of rifaximin-α in this context. METHODS: A survey was conducted of healthcare professionals (HCPs) from Europe and Australia involved in hepatic encephalopathy management. HCPs rated the importance of a range of therapeutic objectives on a 1-7 Likert scale (1 = not at all important; 7 = extremely important). HCPs were also required to provide three patient record forms (PRFs) based on their last three hepatic encephalopathy patients. RESULTS: There were 218 HCP respondents, who provided 654 PRFs (patients treated with rifaximin-α, n = 347; patients not treated with rifaximin-α, n = 307). The mean Likert score was highest for the therapeutic objective 'improving a patient's QoL' (6.4), which was rated significantly more highly than all other therapeutic objectives, including 'reducing the patient's likelihood of hospital readmission' (6.1; P < 0.001) and 'preventing death of the patient' (6.1; P < 0.001). Despite this, only 28.3% of PRFs documented specific QoL data assessment. Patients receiving rifaximin-α were treated later in their disease course than those not receiving rifaximin-α. CONCLUSIONS: HCPs consider QoL improvement the main therapeutic objective in hepatic encephalopathy management, but most do not explicitly assess QoL. Earlier introduction of rifaximin-α may safeguard QoL improvement even when QoL monitoring is not possible.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Design of the Prospective Real-world Outcomes Study of hepatic encephalopathy Patients’ Experience on Rifaximin-α (PROSPER): an observational study among 550 patients

Abstract Background Hepatic encephalopathy (HE) is one of the most important severe complications of liver cirrhosis. Thought to be caused by elevated blood levels of gut-derived neurotoxins (particularly ammonia) entering the brain, HE manifests as a wide range of neurological or psychiatric abnormalities, which increase the risk of mortality, result in substantial morbidity and negatively affect the quality of life (QoL) of both patients and their caregivers. HE is also associated with a substantial economic burden. Rifaximin-α 550 mg is a locally acting oral antibiotic that reduces the effects of ammonia-producing intestinal flora, and which is used to help reduce the recurrence of overt HE. The efficacy of rifaximin-α 550 mg was established in a randomised controlled trial and long-term extension study. However, ‘real-world’ evidence is also required to assess how this efficacy may translate into effectiveness in clinical practice, including the potential impact of treatment on healthcare resource utilisation. Methods The Prospective Real-world Outcomes Study of HE Patients’ Experience on Rifaximin-α 550 mg (PROSPER) is a multinational, multicentre, observational study that will be conducted under real-world clinical practice conditions. Comprising a retrospective phase (up to 12 months) and a prospective phase (up to 24 months), and employing a robust statistical methodology, PROSPER has been specifically designed to minimise the bias associated with observational studies. The primary endpoint will be the effect of rifaximin-α 550 mg treatment on HE- and liver-related hospitalisation rate and duration of hospitalisation. Secondary endpoints will include comprehensive assessments of the impact of treatment on the QoL and workplace productivity of patients and caregivers, a global assessment of treatment effectiveness and safety/tolerability. Approximately 550 patients will be enrolled. Conclusions PROSPER will provide valuable real-world information on the effectiveness of rifaximin-α 550 mg in reducing the recurrence of HE, and its impact on the QoL and work productivity of patients and their caregivers. By providing data on both the direct costs (e.g., hospitalisation rate, duration of hospitalisation) and indirect costs (such as work productivity) of HE, PROSPER should help confirm whether rifaximin-α 550 mg treatment represents a good use of economic resources. Trial registration ClinicalTrials.gov identifier NCT02488993