Vesicles: Looking inside the cell.

Advances in imaging techniques have shed new light on the structure of vesicles formed by COPI protein complexes

Dissection of GTPase activating proteins reveals functional asymmetry in the COPI coat of budding yeast.

The Arf GTPase controls formation of the COPI vesicle coat. Recent structural models of COPI revealed the positioning of two Arf1 molecules in contrasting molecular environments. Each of these pockets for Arf1 is expected to also accommodate an Arf GTPase-activating protein (ArfGAP). Structural evidence and protein interactions observed between isolated domains indirectly suggests that each niche may preferentially recruit one of the two ArfGAPs known to affect COPI, Gcs1/ArfGAP1 and Glo3/ArfGAP2/3, although only partial structures are available. The functional role of the unique non-catalytic domain of either ArfGAP has not been integrated into the current COPI structural model. Here, we delineate key differences in the consequences of triggering GTP hydrolysis via the activity of one versus the other ArfGAP. We demonstrate that Glo3/ArfGAP2/3 specifically triggers Arf1 GTP hydrolysis impinging on the stability of the COPI coat. We show that the yeast homologue of AMP kinase, Snf1, phosphorylates the region of Glo3 that is critical for this effect and thereby regulates its function in the COPI-vesicle cycle. Our results revise the model of ArfGAP function in the molecular context of COPI

Barriers and facilitators to chemotherapy patients' engagement in medical error prevention

Background: Medical errors are a serious threat to chemotherapy patients. Patients can make contributions to safety but little is known about the acceptability of error-preventing behaviors and its predictors. Patients and methods: A cross-sectional survey study among chemotherapy patients treated at the oncology/hematology unit of a regional hospital was conducted. Patients were presented vignettes of errors and unsafe acts and responded to measures of attitudes, behavioral control, norms, barriers, and anticipated reaction. Results: A total of 479 patients completed the survey (52% response rate). Patients reported a high level of anticipated activity but intentions to engage for safety varied considerably between the hypothetical scenarios (range: 57%-96%, χ2 P < 0.001). Health, knowledge and staff time pressure were perceived as most important barriers. Instrumental [odds ratio (OR) = 1.3, P = 0.046] and experiential attitudes (OR = 1.4, P < 0.001), expectations attributed to clinical staff (OR = 1.2, P = 0.024) and behavioral control (OR = 1.8, P < 0.001) were predictors for patients' behaviors. Conclusions: Patients are affirmative toward engaging for safety but perceive considerable barriers. Intentions to engage in error prevention vary by clinical context and are strongly influenced by attitudes, normative and control beliefs. To successfully involve patients in medical error, prevention clinicians need to address their patients' beliefs and reduce barriers through educatio

Registration and Management of "Never Events" in Swiss Hospitals-The Perspective of Clinical Risk Managers.

BACKGROUND In Switzerland, there is no mandatory reporting of "never events." Little is known about how hospitals in countries with no "never event" policies deal with these incidents in terms of registration and analyses. OBJECTIVE The aim of our study was to explore how hospitals outside mandatory "never event" regulations identify, register, and manage "never events" and whether practices are associated with hospital size. METHODS Cross-sectional survey data were collected from risk managers of Swiss acute care hospitals. RESULTS Clinical risk managers representing 95 hospitals completed the survey (55% response rate). Among responding risk and quality managers, only 45% would be formally notified through a designated reporting channel if a "never event" has happened in their hospital. Averaged over a list of 8 specified events, only half of hospitals could report a systematic count of the number of events. Hospital size was not associated with "never event" management. Respondents reported that their hospital pays "too little attention" to the recording (46%), the analysis (34%), and the prevention (40%) of "never events." All respondents rated the systematic registration and analysis of "never events" as very (81%) or rather important (19%) for the improvement of patient safety. CONCLUSIONS A substantial fraction of Swiss hospitals do not have valid data on the occurrence of "never events" available and do not have reliable processes installed for the registration and exam of these events. Surprisingly, larger hospitals do not seem to be better prepared for "never events" management

Speaking up or remaining silent about patient safety concerns in rehabilitation: A cross-sectional survey to assess staff experiences and perceptions.

Background and Aims Patient safety incidents may be prevented if healthcare workers speak up to voice their concerns when they observe hazardous clinical situations. This study aims to investigate the frequency of speaking up and healthcare workers' perception of organizational climate in rehabilitation clinics. Methods An online survey was conducted in five rehabilitation clinics. An existing survey instrument (Speaking Up About Patient Safety Questionnaire [SUPS-Q]) was adapted for this purpose. The instrument includes items on self-reported speak-up-related behavior (perceived safety concerns, withholding voice, and speaking up), anticipated speak-up behavior, barriers to speaking up, and speak-up-related climate measures (psychological safety, encouraging environment, and resignation). Data analysis included descriptive statistics, one-way analysis of variance for differences between groups, multiple regression, and measures for validity and reliability of the scales.\ud Results Four hundred seventy-one individuals participated in the survey (response rate of 32%). In the 4 weeks preceding the survey, 81% of respondents had specific concerns about patient safety, 83% performed speak up and 41% remained silent in one or more instances. Expected differences between professional groups were confirmed, but surprisingly, we found no effect of hierarchical level on speaking up behavior and perception of the speak-up climate. Factors that most frequently prevented healthcare workers from speaking up were ineffectiveness (38%), presence of patients (26%), and unpredictability of the actor's reaction (25%). The psychometric evaluation of the adapted SUPS-Q showed acceptable results for validity and reliability. Conclusions Healthcare workers in rehabilitation clinics frequently perceive safety concerns. The study underlines the importance of promoting a culture of safety and speaking up. The short survey instrument SUPS-Q can be used by rehabilitation clinics to initiate discussions related to facilitators and barriers to speaking up and to identify areas for improvement within the organization

Compliance with the surgical safety checklist in Switzerland: an observational multicenter study based on self-reported data.

BACKGROUND Since publication of the surgical safety checklist by the WHO in 2009, it has been introduced in many hospitals. However, frequency and quality of surgical safety checklist use is often low probably limiting the effectiveness of the checklist in preventing patient harm. The focus of this study was to examine the current state of compliance with the surgical safety checklist in Switzerland and to evaluate how the data relates to international comparative data. METHODS Between November 2020 and March 2021 twelve hospitals with 15 sites collected for at least 200 surgical interventions each whether the three sections of the surgical safety checklist (Sign In, Team Time Out, Sign Out) have been applied. This data collection was part of a large quality improvement project focusing on measuring and improving compliance with the surgical safety checklist via peer observation and feedback. Descriptive statistics were used to analyze the data; chi-square tests were used to compare sub-samples. RESULTS The hospitals collected valid compliance data for 8622 surgical interventions. Mean compliance rate was 91% when distinguishing between the two categories applied (including partially applied) and not applied. In line with previous research, Sign In (93%) and Team Time Out (94%) sections have been applied more frequently than Sign Out (86%). All three surgical safety checklist sections have been applied in 79% of the surgical interventions, no sections in 1%. CONCLUSIONS The results of this study indicate that the overall application of the surgical safety checklist in Switzerland can be considered high, although the completeness, especially of the Sign Out section, could be improved. At present, it seems difficult to compare compliance rates from different studies as measurement methods and definitions of compliance vary widely. A systematization and homogenization of the methodology within, but also beyond, national borders is desirable for the future

Oncology nurses' beliefs and attitudes towards the double-check of chemotherapy medications:a cross-sectional survey study

BACKGROUND: Double-checking medications is a widely used strategy to enhance safe medication administration in oncology, but there is little evidence to support its effectiveness. The proliferated use of double-checking may be explained by positive attitudes towards checking among nurses. This study investigated oncology nurses' beliefs towards double-checking medication, its relation to beliefs about safety and the influence of nurses' level of experience and proximity to clinical care. METHODS: This was a survey of all oncology nurses in three Swiss hospitals. The questionnaire contained 41 items on 6 domains. Responses were recorded using a 7-point Likert scale. Multiple regression analysis was used to identify factors linked to strong beliefs in the effectiveness of double-checking. RESULTS: Overall, 274 (70%) out of 389 nurses responded (91% female, mean age 37 (standard deviation = 10)). Nurses reported very strong beliefs in the effectiveness and utility of double-checking. They were also confident about their own performance in double-checking. Nurses widely believed that double checking produced safety (e.g., 86% believed errors of individuals could be intercepted with double-checks). In contrast, some limitations of double-checking were also recognized, e.g., 33% of nurses reported that double checking caused frequent interruptions and 28% reported that double-checking was done superficially in their unit. Regression analysis revealed that beliefs in effectiveness of double-checking were mainly associated with beliefs in safety production (p < 0.001). Nurses with experience in barcode scanning held less strong beliefs in effectiveness of double-checking (p = 0.006). In contrast to our expectations, there were no differences in beliefs between any professional sub-groups. CONCLUSION: The widespread and strong believe in the effectiveness of double-checking is linked to beliefs about safety production and co-exists with acknowledgement of the major disadvantages of double-checking by humans. These results are important factors to consider when any existing procedures are adapted or new checking procedures are implemented

Regulated targeting of the monotopic hairpin membrane protein Erg1 requires the GET pathway

The guided entry of tail-anchored proteins (GET) pathway targets C-terminally anchored transmembrane proteins and protects cells from lipotoxicity. Here, we reveal perturbed ergosterol production in ∆get3 cells and demonstrate the sensitivity of GET pathway mutants to the sterol synthesis inhibiting drug terbinafine. Our data uncover a key enzyme of sterol synthesis, the hairpin membrane protein squalene monooxygenase (Erg1), as a non-canonical GET pathway client, thus rationalizing the lipotoxicity phenotypes of GET pathway mutants. Get3 recognizes the hairpin targeting element of Erg1 via its classical client-binding pocket. Intriguingly, we find that the GET pathway is especially important for the acute upregulation of Erg1 induced by low sterol conditions. We further identify several other proteins anchored to the endoplasmic reticulum (ER) membrane exclusively via a hairpin as putative clients of the GET pathway. Our findings emphasize the necessity of dedicated targeting pathways for high-efficiency targeting of particular clients during dynamic cellular adaptation and highlight hairpin proteins as a potential novel class of GET clients

Implementation status of safety measures to prevent errors with non-oncologic methotrexate: surveys in community and hospital pharmacies.

BACKGROUND Accidental overdose of low-dose methotrexate can lead to serious patient harm. Different safety measures are recommended to prevent errors, yet, as errors continue to happen, their implementation is questionable. AIM To evaluate the implementation status of safety measures for methotrexate in community and hospital pharmacies. METHOD An electronic questionnaire was sent to head pharmacists of 163 community and 94 hospital pharmacies in Switzerland. The implementation of recommended safety measures (general measures, safety working procedures, IT-based measures) was assessed and descriptive analysis performed. An analysis of sales data underlined the relevance of our results, i.e., the population under risk for overdose. RESULTS A response was obtained from 53% (n = 87) of community and 50% (n = 47) of hospital pharmacists. Pharmacies had implemented a median of 6 (IQR 3, community) and 5 (IQR 5, hospital) safety measures overall. Most of these were defined safety procedures, instructing staff on how to handle methotrexate prescriptions. Across all safety measures, compliance with single procedures was perceived as "very likely" by 54% of community pharmacies. IT-based measures (e.g., alerts) were absent in 38% (n = 31) of community and 57% (n = 27) of hospital pharmacies. On average, every community pharmacy dispensed 22 packages annually. CONCLUSION Safety in relation to methotrexate in pharmacies relies mostly on staff instructions, which are considered weak measures. In light of the serious risk imposed on patients, pharmacies should set a focus on stronger IT-based measures that rely less on human performance

Quality standards for safe medication in nursing homes: development through a multistep approach including a Delphi consensus study.

OBJECTIVES The aim of the study was to develop quality standards reflecting minimal requirements for safe medication processes in nursing homes. DESIGN In a first step, relevant key topics for safe medication processes were deducted from a systematic search for similar guidelines, prior work and discussions with experts. In a second step, the essential requirements for each key topic were specified and substantiated with a literature-based rationale. Subsequently, the requirements were evaluated with a piloted, two-round Delphi study. SETTING Nursing homes in Switzerland. PARTICIPANTS Interprofessional panel of 25 experts from science and practice. PRIMARY AND SECONDARY OUTCOME MEASURES Each requirement was rated for its relevance for a safer and resident-oriented medication on a 9-point Likert-Scale based on the RAND/UCLA method. The requirements were considered relevant if, in the second round, the median relevance rating was ≥7 and the proportion of ratings ≥7 was ≥80%. RESULTS Five key topics with a total of 87 requirements were elaborated and rated in the Delphi study. After the second round (response rate in both rounds 100%), 85 requirements fulfilled the predefined criteria and were therefore included in the final set of quality standards. The five key topics are: (I) 'The medication is reviewed regularly and in defined situations', (II) 'The medication is reviewed in a structured manner', (III) 'The medication is monitored in a structured manner', (IV) 'All healthcare professionals are committed to an optimal interprofessional collaboration' and (V) 'Residents are actively involved in medication process'. CONCLUSIONS We developed normative quality standards for a safer and resident-oriented medication in Swiss nursing homes. Altogether, 85 requirements define the medication processes and the behaviour of healthcare professionals. A rigorous implementation may support nursing homes in taking a step towards safer and resident-oriented medication