Procedural and documentation variations in intravenous infusion administration: a mixed methods study of policy and practice across 16 hospital trusts in England.

BACKGROUND: Procedural and documentation deviations relating to intravenous (IV) infusion administration can have important safety consequences. However, research on such deviations is limited. To address this we investigated the prevalence of procedural and documentation deviations in IV infusion administration and explored variability in policy and practice across different hospital trusts. METHODS: We conducted a mixed methods study. This involved observations of deviations from local policy including quantitative and qualitative data, and focus groups with clinical staff to explore the causes and contexts of deviations. The observations were conducted across five clinical areas (general medicine, general surgery, critical care, paediatrics and oncology day care) in 16 National Health Service (NHS) trusts in England. All infusions being administered at the time of data collection were included. Deviation rates for procedural and documentation requirements were compared between trusts. Local data collectors and other relevant stakeholders attended focus groups at each trust. Policy details and reasons for deviations were discussed. RESULTS: At least one procedural or documentation deviation was observed in 961 of 2008 IV infusions (deviation rate 47.9%; 95% confidence interval 45.5-49.8%). Deviation rates at individual trusts ranged from 9.9 to 100% of infusions, with considerable variation in the prevalence of different types of deviation. Focus groups revealed lack of policy awareness, ambiguous policies, safety and practicality concerns, different organisational priorities, and wide variation in policies and practice relating to prescribing and administration of IV flushes and double-checking. CONCLUSIONS: Deviation rates and procedural and documentation requirements varied considerably between hospital trusts. Our findings reveal areas where local policy and practice do not align. Some policies may be impractical and lack utility. We suggest clearer evidence-based standardisation and local procedures that are contextually practical to address these issues.

Errors and discrepancies in the administration of intravenous infusions: a mixed methods multihospital observational study.

INTRODUCTION: Intravenous medication administration has traditionally been regarded as error prone, with high potential for harm. A recent US multisite study revealed few potentially harmful errors despite a high overall error rate. However, there is limited evidence about infusion practices in England and how they relate to prevalence and types of error. OBJECTIVES: To determine the prevalence, types and severity of errors and discrepancies in infusion administration in English hospitals, and to explore sources of variation, including the contribution of smart pumps. METHODS: We conducted an observational point prevalence study of intravenous infusions in 16 National Health Service hospital trusts. Observers compared each infusion against the medication order and local policy. Deviations were classified as errors or discrepancies based on their potential for patient harm. Contextual issues and reasons for deviations were explored qualitatively during observer debriefs. RESULTS: Data were collected from 1326 patients and 2008 infusions. Errors were observed in 231 infusions (11.5%, 95% CI 10.2% to 13.0%). Discrepancies were observed in 1065 infusions (53.0%, 95% CI 50.8% to 55.2%). Twenty-three errors (1.1% of all infusions) were considered potentially harmful; none were judged likely to prolong hospital stay or result in long-term harm. Types and prevalence of errors and discrepancies varied widely among trusts, as did local policies. Deviations from medication orders and local policies were sometimes made for efficiency or patient need. Smart pumps, as currently implemented, had little effect, with similar error rates observed in infusions delivered with and without a smart pump (10.3% vs 10.8%, p=0.8). CONCLUSION: Errors and discrepancies are relatively common in everyday infusion administrations but most have low potential for patient harm. Better understanding of performance variability to strategically manage risk may be a more helpful tactic than striving to eliminate all deviations.

Ki-67 index and response to chemotherapy in patients with neuroendocrine tumours.

Chemotherapy (CT) is widely used for neuroendocrine tumours (NETs), but there are no validated biomarkers to predict response. The Ki-67 proliferation index has been proposed as a means of selecting patients for CT, but robust data are lacking. The aim of this study was to investigate the relationship between response to chemotherapy and Ki-67 in NET. We reviewed data from 222 NET patients treated with CT. Tumours were graded according to Ki-67 index: G1 ≤2%, G2 3-20% and G3 >20%. Response was assessed according to RECIST and survival calculated from start of chemotherapy to death. To explore Ki-67 as a marker of response, we calculated the likelihood ratio and performed receiver operating characteristic analysis. Overall, 193 patients had a documented Ki-67 index, of which 173 were also evaluable for radiological response: 10% were G1, 46% G2 and 43% G3; 46% were pancreatic NET (PNET). Median overall survival was 22.1 months. Overall response rate was 30% (39% in PNET vs 22% in non-PNET) and 43% of patients had stable disease. Response rate increased with grade: 6% in G1 tumours, 24% in G2 and 43% in G3. However, maximum likelihood ratio was 2.3 at Ki-67=35%, and the area under the ROC curve was 0.60. As reported previously, a high Ki-67 was an adverse prognostic factor for overall survival. In conclusion, response to CT increases with Ki-67 index, but Ki-67 alone is an unreliable means to select patients for CT. Improved methods to stratify patients for systemic therapy are required.

Exploring the Current Landscape of Intravenous Infusion Practices and Errors (ECLIPSE): protocol for a mixed-methods observational study.

INTRODUCTION: Intravenous medication is essential for many hospital inpatients. However, providing intravenous therapy is complex and errors are common. 'Smart pumps' incorporating dose error reduction software have been widely advocated to reduce error. However, little is known about their effect on patient safety, how they are used or their likely impact. This study will explore the landscape of intravenous medication infusion practices and errors in English hospitals and how smart pumps may relate to the prevalence of medication administration errors. METHODS AND ANALYSIS: This is a mixed-methods study involving an observational quantitative point prevalence study to determine the frequency and types of errors that occur in the infusion of intravenous medication, and qualitative interviews with hospital staff to better understand infusion practices and the contexts in which errors occur. The study will involve 5 clinical areas (critical care, general medicine, general surgery, paediatrics and oncology), across 14 purposively sampled acute hospitals and 2 paediatric hospitals to cover a range of intravenous infusion practices. Data collectors will compare each infusion running at the time of data collection against the patient's medication orders to identify any discrepancies. The potential clinical importance of errors will be assessed. Quantitative data will be analysed descriptively; interviews will be analysed using thematic analysis. ETHICS AND DISSEMINATION: Ethical approval has been obtained from an NHS Research Ethics Committee (14/SC/0290); local approvals will be sought from each participating organisation. Findings will be published in peer-reviewed journals and presented at conferences for academic and health professional audiences. Results will also be fed back to participating organisations to inform local policy, training and procurement. Aggregated findings will inform the debate on costs and benefits of the NHS investing in smart pump technology, and what other changes may need to be made to ensure effectiveness of such an investment.

Understanding safety-critical interactions with a home medical device through Distributed Cognition.

As healthcare shifts from the hospital to the home, it is becoming increasingly important to understand how patients interact with home medical devices, to inform the safe and patient-friendly design of these devices. Distributed Cognition (DCog) has been a useful theoretical framework for understanding situated interactions in the healthcare domain. However, it has not previously been applied to study interactions with home medical devices. In this study, DCog was applied to understand renal patients' interactions with Home Hemodialysis Technology (HHT), as an example of a home medical device. Data was gathered through ethnographic observations and interviews with 19 renal patients and interviews with seven professionals. Data was analyzed through the principles summarized in the Distributed Cognition for Teamwork methodology. In this paper we focus on the analysis of system activities, information flows, social structures, physical layouts, and artefacts. By explicitly considering different ways in which cognitive processes are distributed, the DCog approach helped to understand patients' interaction strategies, and pointed to design opportunities that could improve patients' experiences of using HHT. The findings highlight the need to design HHT taking into consideration likely scenarios of use in the home and of the broader home context. A setting such as home hemodialysis has the characteristics of a complex and safety-critical socio-technical system, and a DCog approach effectively helps to understand how safety is achieved or compromised in such a system.

Exploring medical device design and use through layers of distributed cognition: how a glucometer is coupled with its context.

Medical devices are becoming more interconnected and complex, and are increasingly supported by fragmented organizational systems, e.g. through different processes, committees, supporting staff and training regimes. Distributed Cognition has been proposed as a framework for understanding the design and use of medical devices. However, it is not clear that it has the analytic apparatus to support the investigation of such complexities. This paper proposes a framework that introduces concentric layers to DiCoT, a method that facilitates the application of Distributed Cognition theory. We use this to explore how an inpatient blood glucose meter is coupled with its context. The analysis is based on an observational study of clinicians using a newly introduced glucometer on an oncology ward over approximately 150h (11days and 4 nights). Using the framework we describe the basic mechanics of the system, incremental design considerations, and larger design considerations. The DiCoT concentric layers (DiCoT-CL) framework shows promise for analyzing the design and use of medical devices, and how they are coupled with their context.

Patients' and carers' experiences of interacting with home haemodialysis technology: implications for quality and safety.

BACKGROUND: Little is known about patients' and carers' experiences of interacting with home haemodialysis (HHD) technology, in terms of user experience, how the design of the technology supports safety and fits with home use, and how the broader context of service provision impacts on patients' use of the technology. METHODS: Data were gathered through ethnographic observations and interviews with 19 patients and their carers associated with four different hospitals in the UK, using five different HHD machines. All patients were managing their condition successfully on HHD. Data were analysed qualitatively, focusing on themes of how individuals used the machines and how they managed their own safety. RESULTS: Findings are organised by three themes: learning to use the technology, usability of the technology, and managing safety during dialysis. Home patients want to live their lives fully, and value the freedom and autonomy that HHD gives them; they adapt use of the technology to their lives and their home context. They also consider the machines to be safe; nevertheless, most participants reported feeling scared and having to learn through mistakes in the early months of dialysing at home. Home care nurses and technicians provide invaluable support. Although participants reported on strategies for anticipating problems and keeping safe, perceived limitations of the technology and of the broader system of care led some to trade off safety against immediate quality of life. CONCLUSIONS: Enhancing the quality and safety of the patient experience in HHD involves designing technology and the broader system of care to take account of how individuals manage their dialysis in the home. Possible design improvements to enhance the quality and safety of the patient experience include features to help patients manage their dialysis (e.g. providing timely reminders of next steps) and features to support communication between families and professionals (e.g. through remote monitoring).

Oxaliplatin/5-fluorouracil in advanced hepatocellular carcinoma: case report and single-center retrospective review.

AIMS: Sorafenib is the only standard therapy for advanced hepatocellular carcinoma, but has a low response rate. Leucovorin and oxaliplatin (FOLFOX) has a superior response rate versus doxorubicin among Asian sorafenib-naive patients. We aimed to retrospectively review the outcome of 20 consecutive patients treated with FOLFOX at a single European center. MATERIALS & METHODS: Patients had symptomatic disease burdens unlikely to regress with sorafenib or had no proven treatment options (sorafenib-refractory or recurrence post liver transplantation). RESULTS: One sorafenib-refractory patient had a complete response and two liver transplant patients experienced partial responses. Median overall survival was 6.3 months. There was one chemotherapy death due to neutropenic sepsis. CONCLUSION: In advanced hepatocellular carcinoma, FOLFOX can induce clinically relevant responses, but needs prospective validation.

7 Themes for guiding situated ergonomic assessments of medical devices: a case study of an inpatient glucometer.

There is relatively little guidance on the situated ergonomic assessment of medical devices, and few case studies that detail this type of evaluation. This paper reports results of a detailed case study that focuses on the design and use of a modern blood glucose meter on an oncology ward. We spent approximately 150 h in-situ, over 11 days and 4 nights, performing observations and interviews with users. This was complemented by interviews with two staff with oversight and management responsibility related to the device. We identified 19 issues with the design and use of this device. These issues were grouped into 7 themes which can help guide the situated study of medical devices: usability, knowledge gaps and mental models, workarounds, wider tasks and equipment, the patient, connection between services, and policy.

A phase I study of single administration of antibody-directed enzyme prodrug therapy with the recombinant anti-carcinoembryonic antigen antibody-enzyme fusion protein MFECP1 and a bis-iodo phenol mustard prodrug.

PURPOSE: Antibody-directed enzyme prodrug therapy is a two-stage treatment whereby a tumor-targeted antibody-enzyme complex localizes in tumor for selective conversion of prodrug. The purpose of this study was to establish optimal variables for single administration of MFECP1, a recombinant antibody-enzyme fusion protein of an anti-carcinoembryonic antigen single-chain Fv antibody and the bacterial enzyme carboxypeptidase G2 followed by a bis-iodo phenol mustard prodrug. MFECP1 is manufactured in mannosylated form to facilitate normal tissue elimination. EXPERIMENTAL DESIGN: Pharmacokinetic, biodistribution, and tumor localization studies were used to test the hypothesis that MFECP1 localizes in tumor and clears from normal tissue via the liver. Firstly, safety of MFECP1 and a blood concentration of MFECP1 that would avoid systemic prodrug activation were tested. Secondly, dose escalation of prodrug was done. Thirdly, the dose of MFECP1 and timing of prodrug administration were optimized. RESULTS: MFECP1 was safe and well tolerated, cleared rapidly via the liver, and was less immunogenic than previously used products. Eighty-fold dose escalation from the starting dose of prodrug was carried out before dose-limiting toxicity occurred. Confirmation of the presence of enzyme in tumor and DNA interstrand cross-links indicating prodrug activation were obtained for the optimal dose and time point. A total of 28 of 31 patients was evaluable for response, the best response being a 10% reduction of tumor diameter, and 11 of 28 patients had stable disease. CONCLUSIONS: Optimal conditions for effective therapy were established. A study testing repeat treatment is currently being undertaken.

Overcoming the immunologic response to foreign enzymes in cancer therapy.

Foreign enzymes play a part in a variety of cancer treatments and have the potential for a much greater role. In most cases, repeated administration of the enzyme is required for effective therapy, however, this can be restricted by undesirable effects caused by immunogenicity. Repeated or prolonged treatment can lead to an antibody response, and this may neutralize the enzyme and prevent it from remaining in the circulation. Ultimately, this can lead to a diminished therapeutic effect and increase the risk of infusion reactions. More insidiously, there is a danger that antibodies will not only neutralize the foreign enzyme, but will crossreact with a vital component in normal tissue. Such responses can damage normal tissues and give rise to serious clinical syndromes. The aim for enzymes in cancer therapy is to allow repeated treatments without compromising safety or efficacy. This can potentially be achieved by understanding and controlling the immune response and by modifying the enzyme accordingly. A crucial requirement, and one that is particularly challenging for enzymes to achieve, is that the modifications introduced do not interfere with structure, function or stability.

Engineering antibodies for clinical applications in cancer.

The 'magic bullet' concept predicted over a century ago that antibodies would be used to target cancer therapy. Since then initial problems that were related to specificity, purity and immungenicity of antibody-based reagents have slowly been overcome due to developments in technology and increased knowledge. As a result, antibodies are in use for many clinical applications and now comprise the second largest category of medicines in clinical development after vaccines. For antibody-based cancer therapeutics the last 20 years have met with an explosion of knowledge about the biology of the disease and potential targets as well as new technology which allows cloning and manipulation of multifunctional antibody-based molecules. However, the focus still remains on developing therapeutics that will have potential for treating cancer in people and this is efficiently assessed in mechanistic clinical trials that feed back to the laboratory for further development. This review illustrates the mechanistic approach to making new molecules for antibody imaging and therapy of cancer. It is illustrated by examples of radioimmunotherapy and antibody-directed enzyme prodrug therapy developed by the authors.