Stability indicating ion-pair reversed-phase liquid chromatography method for modified mRNA.

Modified messenger RNA (mRNA) represents a rapidly emerging class of therapeutic drug product. Development of robust stability indicating methods for control of product quality are therefore critical to support successful pharmaceutical development. This paper presents an ion-pair reversed-phase liquid chromatography (IP-RPLC) method to characterise modified mRNA exposed to a wide set of stress-inducing conditions, relevant for pharmaceutical development of an mRNA drug product. The optimised method could be used for separation and analysis of large RNA, sized up to 1000 nucleotides. Column temperature, mobile phase flow rate and ion-pair selection were each studied and optimised. Baseline separations of the model RNA ladder sample were achieved using all examined ion-pairing agents. We established that the optimised method, using 100 mM Triethylamine, enabled the highest resolution separation for the largest fragments in the RNA ladder (750/1000 nucleotides), in addition to the highest overall resolution for the selected modified mRNA compound (eGFP mRNA, 996 nucleotides). The stability indicating power of the method was demonstrated by analysing the modified eGFP mRNA, upon direct exposure to heat, hydrolytic conditions and treatment with ribonucleases. Our results showed that the formed degradation products, which appeared as shorter RNA fragments in front of the main peak, could be well monitored, using the optimised method, and the relative stability of the mRNA under the various stressed conditions could be assessed.

The Storage and In-Use Stability of mRNA Vaccines and Therapeutics: Not A Cold Case.

The remarkable impact of mRNA vaccines on mitigating disease and improving public health has been amply demonstrated during the COVID-19 pandemic. Many new mRNA-based vaccine and therapeutic candidates are in development, yet the current reality of their stability limitations requires their frozen storage. Numerous challenges remain to improve formulated mRNA stability and enable refrigerator storage, and this review provides an update on developments to tackle this multi-faceted stability challenge. We describe the chemistry underlying mRNA degradation during storage and highlight how lipid nanoparticle (LNP) formulations are a double-edged sword: while LNPs protect mRNA against enzymatic degradation, interactions with and between LNP excipients introduce additional risks for mRNA degradation. We also discuss strategies to improve mRNA stability both as a drug substance (DS) and a drug product (DP) including the (1) design of the mRNA molecule (nucleotide selection, primary and secondary structures), (2) physical state of the mRNA-LNP complexes, (3) formulation composition and purity of the components, and (4) DS and DP manufacturing processes. Finally, we summarize analytical control strategies to monitor and assure the stability of mRNA-based candidates, and advocate for an integrated analytical and formulation development approach to further improve their storage, transport, and in-use stability profiles.

A scoping review of the incentives for a prolonged work life after pensionable age and the importance of "bridge employment".

BACKGROUND: With a growing share of older people in almost every population, discussions are being held worldwide about how to guarantee welfare in the immediate future. Different solutions are suggested, but in this article the focus is on the need to keep older employees active in the labor market for a prolonged time. OBJECTIVE: The aim was to find out and describe the incentives at three system levels for older people 1) wanting, 2) being able, and 3) being allowed to work. MATERIAL: The literature search embraced articles from the databases Scopus, PsycInfo, Cinahl, AgeLine and Business Source Premier, from May 2004 until May 2016. After the removal of 506 duplicates, the selection and analysis started with the 1331 articles that met the search criteria. Of these, 58 articles corresponded with the research questions. METHOD: The design was a 'scoping review' of the research area bridge employment and prolonged work life. RESULTS: The results show that most investigations are conducted on individual-level predictors, research on organizational-level predictors is more scattered, and societal-level predictor information is scarce. CONCLUSIONS: Attitudes and behavior according to a prolonged work life could be summarized as dependent on good health, a financial gain in combination with flexible alternative working conditions.

Designing flexible low-viscous sieving media for capillary electrophoresis analysis of ribonucleic acids.

Modified messenger RNA (mRNA) has recently become a new prospective class of drug product. Consequently, stability indicating separation methods are needed to progress pharmaceutical development of mRNA. A promising separation technique for the analysis of mRNA is capillary gel electrophoresis (CGE). We designed a flexible, low-viscous sieving medium for CGE, based on high mass linear polyvinylpyrrolidone (PVP) and glycerol. A Central Composite Face-centered design resulted in a strong model that allowed us to predict suitable sieving media compositions by using multi-objective optimization. The way of working proposed in this paper gives analysts the freedom to design a suitable sieving medium for their response(s) of interest, for purity and stability analysis of polynucleotides with a size around 100-1000 bases. Depending on the criteria for the analysis there will be a trade-off between different suitable conditions. By using this method, we created a sieving medium that was able to improve resolution, peak height and analysis time of an RNA ladder compared to the current commercially available separation gels.

Vital sign documentation in electronic records: The development of workarounds.

Workarounds are commonplace in healthcare settings. An increase in the use of electronic health records has led to an escalation of workarounds as healthcare professionals cope with systems which are inadequate for their needs. Closely related to this, the documentation of vital signs in electronic health records has been problematic. The accuracy and completeness of vital sign documentation has a direct impact on the recognition of deterioration in a patient's condition. We examined workflow processes to identify workarounds related to vital signs in a 372-bed hospital in Sweden. In three clinical areas, a qualitative study was performed with data collected during observations and interviews and analysed through thematic content analysis. We identified paper workarounds in the form of handwritten notes and a total of eight pre-printed paper observation charts. Our results suggested that nurses created workarounds to allow a smooth workflow and ensure patients safety.

Recording signs of deterioration in acute patients: The documentation of vital signs within electronic health records in patients who suffered in-hospital cardiac arrest.

Vital sign documentation is crucial to detecting patient deterioration. Little is known about the documentation of vital signs in electronic health records. This study aimed to examine documentation of vital signs in electronic health records. We examined the vital signs documented in the electronic health records of patients who had suffered an in-hospital cardiac arrest and on whom cardiopulmonary resuscitation was attempted between 2007 and 2011 (n = 228), in a 372-bed district general hospital. We assessed the completeness of vital sign data compared to VitalPAC™ Early Warning Score and the location of vital signs within the electronic health records. There was a noticeable lack of completeness of vital signs. Vital signs were fragmented through various sections of the electronic health records. The study identified serious shortfalls in the representation of vital signs in the electronic health records, with consequential threats to patient safety.

Using advanced mobile devices in nursing practice--the views of nurses and nursing students.

Advanced mobile devices allow registered nurses and nursing students to keep up-to-date with expanding health-related knowledge but are rarely used in nursing in Sweden. This study aims at describing registered nurses' and nursing students' views regarding the use of advanced mobile devices in nursing practice. A cross-sectional study was completed in 2012; a total of 398 participants replied to a questionnaire, and descriptive statistics were applied. Results showed that the majority of the participants regarded an advanced mobile device to be useful, giving access to necessary information and also being useful in making notes, planning their work and saving time. Furthermore, the advanced mobile device was regarded to improve patient safety and the quality of care and to increase confidence. In order to continuously improve the safety and quality of health care, advanced mobile devices adjusted for nursing practice should be further developed, implemented and evaluated in research.

Strengths and weaknesses of working with the Global Trigger Tool method for retrospective record review: focus group interviews with team members.

OBJECTIVES: The aim was to describe the strengths and weaknesses, from team member perspectives, of working with the Global Trigger Tool (GTT) method of retrospective record review to identify adverse events causing patient harm. DESIGN: A qualitative, descriptive approach with focus group interviews using content analysis. SETTING: 5 Swedish hospitals in 2011. PARTICIPANTS: 5 GTT teams, with 5 physicians and 11 registered nurses. INTERVENTION: 5 focus group interviews were carried out with the five teams. Interviews were taped and transcribed verbatim. RESULTS: 8 categories emerged relating to the strengths and weaknesses of the GTT method. The categories found were: Usefulness of the GTT, Application of the GTT, Triggers, Preventability of harm, Team composition, Team tasks, Team members' knowledge development and Documentation. Gradually, changes in the methodology were made by the teams, for example, the teams reported how the registered nurses divided up the charts into two sets, each being read respectively. The teams described the method as important and well functioning. Not only the most important, but also the most difficult, was the task of bringing the results back to the clinic. The teams found it easier to discuss findings at their own clinics. CONCLUSIONS: The GTT method functions well for identifying adverse events and is strengthened by its adaptability to different specialties. However, small, gradual methodological changes together with continuingly developed expertise and adaption to looking at harm from a patient's perspective may contribute to large differences in assessment over time.

Nursing students' experience of using a personal digital assistant (PDA) in clinical practice - an intervention study.

BACKGROUND: A personal digital assistant (PDA) is a multifunctional information and communication tool allowing nursing students to keep up to date with expanding health related knowledge. OBJECTIVES: This study was aimed at exploring nursing students' experience of using a PDA in clinical practice. METHOD: In this intervention study, nursing students (n=67) used PDAs during a period of 15 weeks, replied to questionnaires, and participated in focus group interviews. RESULTS: The PDA was found to support nursing students in clinical practice and to have the potential to be a useful tool with benefits for both the patients and for the students. The PDA was regarded as useful, and was presumed to imply increased confidence and time savings, and contribute to improved patient safety and quality of care. CONCLUSIONS: With available mobile technology, nursing students would be able to access necessary information, independent of time and place. Therefore, it is important that stakeholders and educators facilitate the use of PDAs to support nursing students during their clinical practice, in order to prepare them for their future work, and to continuously improve the safety and quality of healthcare.

Nurses' perceptions of an electronic patient record from a patient safety perspective: a qualitative study.

AIMS: The overall aim of this study was to explore nurses' perceptions of using an electronic patient record in everyday practice, in general ward settings. This paper reports on the patient safety aspects revealed in the study. BACKGROUND: Electronic patient records are widely used and becoming the main method of nursing documentation. Emerging evidence suggests that they fail to capture the essence of clinical practice and support the most frequent end-users: nurses. The impact of using electronic patient records in general ward settings is under-explored. METHOD: In 2008, focus group interviews were conducted with 21 Registered Nurses. This was a qualitative study and the data were analysed by content analysis. At the time of data collection, the electronic patient record system had been in use for approximately 1 year. FINDINGS: The findings related to patient safety were clustered in one main category: 'documentation in everyday practise'. There were three sub-categories: vital signs, overview and medication module. Nurses reported that the electronic patient record did not support nursing practice when documenting crucial patient information, such as vital signs. CONCLUSIONS: Efforts should be made to include the views of nurses when designing an electronic patient record to ensure it suits the needs of nursing practice and supports patient safety. Essential patient information needs to be easily accessible and give support for decision-making.

Experience of using a personal digital assistant in nursing practice - a single case study.

AIM: The aim of this study was to describe one nurse's experience of using a personal digital assistant (PDA) in nursing practice. BACKGROUND: Nurses handle large amounts of information and a PDA may contain valuable information that nurses need in their daily work. METHODS: In this qualitative single case study, data were collected through an open-ended interview with one registered nurse and were analysed by content analysis. RESULTS: The findings show that the PDA provides immediate access to information anywhere and at anytime, with advantages for both the nurse and for her patients. The PDA increased her confidence and efficiency in practice; it was easier to keep up-to-date and spend more time with the patient. Furthermore, the PDA was perceived as improving patient safety and patient participation. CONCLUSIONS: The PDA requires improved content and more functions. Ease of use should also be improved. This study indicates that PDAs could be valuable and may inspire further research. IMPLICATIONS FOR NURSING MANAGEMENT: The incorporation of a multifunctional PDA is an important issue for nursing management, as it could both change and provide new possibilities for nursing practice. The use of PDAs could also aid decision-making, improve patient safety and benefit patient outcomes.

Nurses' experience of using electronic patient records in everyday practice in acute/inpatient ward settings: A literature review.

Electronic patient record (EPR) systems have a huge impact on nursing documentation. Although the largest group of end-users of EPRs, nurses have had minimal input in their design. This study aimed to review current research on how nurses experience using the EPR for documentation. A literature search was conducted in Medline and Cinahl of original, peer-reviewed articles from 2000 to 2009, focusing on nurses in acute/ inpatient ward settings. After critical assessment, two quantitative and three qualitative articles were included in the study. Results showed that nurses experience widespread dissatisfaction with systems. Current systems are not designed to meet the needs of clinical practice as they are not user-friendly, resulting in a potentially negative impact on individualized care and patient safety. There is an urgent need for nurses to be directly involved in software design to ensure that the essence and complexity of nursing is not lost in the system.

Personal digital assistant with a barcode reader--a medical decision support system for nurses in home care.

INTRODUCTION: Inappropriate medication among elderly people increases the risk of adverse drug-drug interactions, drug-related falls and hospital admissions. In order to prevent these effects it is necessary to obtain a profile of the patients' medication. A personal digital assistant (PDA) can be used as a medical decision support system (MDSS) to obtain a profile of the patients' medication and to check for inappropriate drugs and drug combinations, and to reduce medication errors. AIM: The aim of the present study was to evaluate nurses' experiences of using a MDSS in a PDA with a barcode reader, in order to obtain profiles of the patients' medication, regarding drug-drug interactions, therapeutic duplications, and warnings for drugs unsuitable for elderly in home care. METHODS: The LIFe-reader is a MDSS in a PDA with a barcode reader. By scanning the drug packages in the patients' home, the LIFe-reader obtained profiles of the patients' medication and checked for drug-drug interactions, therapeutic duplications and warnings for drugs unsuitable for elderly people. The LIFe-reader also contained, e.g. drug information and medical reference works. Nurses (n=15) used the LIFe-reader for five weeks during their nursing home care practice assignment. The nurses answered questionnaires about the content and functions of the LIFe-reader before, during and after the nursing home care practice assignment, and were interviewed in focus groups. Descriptive statistics were used and content analysis was applied for qualitative data. RESULTS: By using the LIFe-reader, the majority of the nurses found it easy to obtain profiles of the patients' medication and check for drug-drug interactions, therapeutic duplications and warnings for drugs unsuitable for elderly people. Most nurses regarded the LIFe-reader to reduce drug-related risks of falling, and some thought it could reduce the drug-related admissions to hospitals. The scanning function was described as easy and time saving, although not always possible to use. The LIFe-reader was regarded as a useful and user-friendly MDSS, but more content and functions were requested. CONCLUSIONS: We found that the LIFe-reader has the potential to be a useful and user-friendly MDSS for nurses in home care when obtaining profiles of the patients' medication regarding drug-drug interactions, therapeutic duplications and warnings for drugs unsuitable for elderly. A regular scanning of the patients' drugs in their home might support nurses and general practitioners (GPs) in reducing the inappropriate use of drugs. If the LIFe-reader should be used in a larger scale among nurses, more content and functions are necessary.

Feasibility of a computerized male urethral catheterization simulator.

Catheterization of the male urethra might cause harm and discomfort for the patient. Computer-based simulator training might improve the skills of students as well as professional nurses. This study aims to study the feasibility of a new portable computer-based male urethral catheterization simulator, Urecath (Melerit Urecath Vision). The simulator consists of three software modules: teaching (explains the different procedures in the catheterization), learning (game settings with practice and self-assessments tests), and simulator module that is connected to a box with a model of a penis where syringes and the urinary catheter can be inserted. Registered nurses (n=23), nurse assistants (n=14), nurse students (n=12), and a nurse assistant student (n=1) participated in a simulation session and answered 30 questions about the feasibility of the simulator. The participants appreciated the different modules, particularly the teaching and learning modules. The simulator module was appreciated for its cross-sectional views and feedback but was found to lack a tactile component; there was too little and no varying resistance when inserting the catheter. The participants perceived the present prototype of Urecath as a valuable education tool. The male urethral catheterization simulator prototype Urecath has advantages in its present shape but to be an alternative to existing training options for practicing male urethral catheterization, it should be complemented with a tactile mode and degrees of difficulty.

A mobile medicine decision support system for district nurses.

Inappropriate use of medicines increases the risk of hospital admissions for the elderly. Not only does this lead to unnecessary suffering for the patients but also incurs a great financial cost to the society. A medicine decision support system in a Personal Digital Assistant (PDA), with a barcode reader, can provide an overview of the patients' complete medicine use, and detect unsuitable drugs and drug combinations. Focusing on the elderly, our aim was to evaluate if a mobile medicine decision support system with a barcode reader is useful and user-friendly for nurses in home care. The participants received a comprehensive overview from the patients' medicine use and noted drug-drug interactions, therapeutic duplications and warnings for drugs unsuitable for elderly people. The nurses regarded that the decision support system increased prevention and safety, was useful and user-friendly. Our findings suggest that most of the content and functions were regarded as important. Therefore, this decision support system might be a useful tool for district nurses.

Nursing informatics in Sweden - the agenda for the future.

With the purpose of getting an overview of the current research and development in information systems and terminology for nursing practice and outline strategies for the future, an initiative for a workshop was taken at the national level in Sweden by the Section for Nursing Informatics, the Society of Nursing and the Association of Health Professionals in 2007. For the workshop around 30 nurses were invited, representing clinical practice, education, and research. The workshop resulted in recommendations for future strategies to support the development of nursing informatics in Sweden.

Disabled persons and the labor market in Sweden.

Persons with disabilities have well-documented problems entering the labor market all over the world. Research reveals that legislation to assist such individuals has relatively less significance than the attitudes of individual employers. In Jonkoping, Sweden, a smaller town of about 120,000 inhabitants, about 100 openings for jobs are created annually for people with learning disabilities and reduced employment capacity. Despite difficulties, local labor market agencies succeed to a relatively great extent, to find real and lasting jobs. An intervention often used for these individuals in Sweden is called Special Introduction and Follow-up Support (SIUS). The purpose of this paper is to provide balance to the somewhat biased but dominant view of persons with disabilities and unemployability. This is contradicted by Swedish data showing that it is possible to find jobs for people with disabilities with the support by trained of SIUS advisers.

The subject of pedagogy from theory to practice--the view of newly registered nurses.

The aim was to describe, from the newly registered nurses' perspective, specific events when using their pedagogical knowledge in their everyday clinical practice. The design was qualitative and the critical incident technique was used. Data was collected via interviews with ten newly registered nurses who graduated from the same University program 10 months earlier and are now employed at a university hospital. Two categories emerged in the analyses. The first category was "Pedagogical methods in theory" with the sub-categories Theory and the application of the course in practice, Knowledge of pedagogy and Information as a professional competence. The second category was "Pedagogical methods in everyday clinical practice" with sub-categories Factual knowledge versus pedagogical knowledge, Information and relatives, Difficulties when giving information, Understanding information received, Pedagogical tools, Collaboration in teams in pedagogical situations, and Time and giving information. By identifying specific events regarding pedagogical methods the findings can be useful for everyone from teachers and health-care managers to nurse students and newly registered nurses, to improve teaching methods in nurse education.

The use of the Personal Digital Assistant (PDA) among personnel and students in health care: a review.

BACKGROUND: Health care personnel need access to updated information anywhere and at any time, and a Personal Digital Assistant (PDA) has the potential to meet these requirements. A PDA is a mobile tool which has been employed widely for various purposes in health care practice, and the level of its use is expected to increase. Loaded with suitable functions and software applications, a PDA might qualify as the tool that personnel and students in health care need. In Sweden today, despite its leadership role in mobile technologies, PDAs are not commonly used, and there is a lack of suitable functions and software applications. OBJECTIVE: The aim of the present review was to obtain an overview of existing research on the use of PDAs among personnel and students in health care. METHODS: The literature search included original peer-reviewed research articles written in English and published from 1996 to 2008. All study designs were considered for inclusion. We excluded reviews and studies focusing on the use of PDAs in classroom situations. From March 2006 to the last update in May 2008, we searched PubMed, CINAHL, Cochrane, IngentaConnect, and a local search engine (ELIN@Kalmar). We conducted a content analysis, using Nielsen's Model of System Acceptability as a theoretical framework in structuring and presenting the results. RESULTS: From the 900 references initially screened, 172 articles were selected and critically assessed until 48 articles remained. The majority originated in North-America (USA: n=24, Canada: n=11). The categories which emerged from our content analysis coincided to a certain extent to Nielsen's Model of System Acceptability (social and practical acceptability), including usefulness (utility and usability) subcategories such as learnability, efficiency, errors, and satisfaction. The studies showed that health care personnel and students used PDAs in patient care with varied frequency. Most of the users were physicians. There is some evidence that the use of a PDA in health care settings might improve decision-making, reduce the numbers of medical errors, and enhance learning for both students and professionals, but the evidence is not strong, with most studies being descriptive, and only 6 randomized controlled trials. Several special software programs have been created and tested for PDAs, and a wide range of situations for their use have been reported for different patient groups. Drug and medical information were commonly accessed by PDA users, and the PDA was often viewed as the preferred tool when compared to paper-based documents. Some users regarded the PDA easy to operate, while others found it difficult in the beginning. CONCLUSIONS: This overview of the use of PDAs revealed a positive attitude towards the PDA, which was regarded as a feasible and convenient tool. The possibility of immediate access to medical information has the potential to improve patient care. The PDA seems to be a valuable tool for personnel and students in health care, but there is a need for further intervention studies, randomized controlled trials, action research, and studies with various health care groups in order to identify its appropriate functions and software applications.

Health care consumers' experiences of information communication technology--a summary of literature.

BACKGROUND: There is an increasing interest in reaching consumers directly through the Internet and different telecommunication systems. The most important contacts in health care will always be the face-to-face meetings, but the tools of health informatics can be seen as a means to an end, which is to provide the best possible health care. A variety of applications have been described in different references. To our knowledge there has been no review of a research-based state of the art in the field of consumers' experiences in using different applications in health informatics. According to the benefits in using information communication technology (ICT) as being cost-effective and timesaving it is of great importance to focus on and examine consumers' experiences. It is important that it is user friendly and regarded as valuable and useful. AIM: The aim of this study was to describe consumers' subjective experiences of using electronic resources with reference to health and illness. DESIGN AND/OR METHOD: A systematic literature search was performed in databases CINAHL, Medline and Cochrane, as well as a manual search. Retrieved references (n=14) were appraised according to their scientific structure and quality. A broad search was performed in order to find as many different applications as possible. Our primary intention was to identify existing references describing consumers' experiences with ICT. RESULTS: In spite of this broad search few references were found. Twelve references remained and three themes were identified: support and help, education and information, and telecommunication instead of on-site visiting. Consumers felt more confident and empowered, their knowledge increased and their health status improved due to the ICT resources. Lack of face-to-face meetings or privacy did not appear to be a problem. CONCLUSION: ICT can improve the nurse-patient relationship and augment well-being for consumers. More research is needed to measure consumers' experiences and factors that influence it.