Development of and adherence to an ERAS® and prehabilitation protocol for patients undergoing pancreatic surgery: An observational study.

BACKGROUND AND OBJECTIVE: There are still gaps in knowledge concerning the adherence to different multimodal pathways in pancreatic surgery. The aim of this trial was to explore and evaluate an Enhanced Recovery After Surgery (ERAS®) and prehabilitation protocol in patients undergoing open pancreatic surgery. METHODS: Three groups of patients were included: two prospective series of 75 patients undergoing open pancreatic surgery following an ERAS® protocol with or without prehabilitation, and one group of 55 historical controls. Variables regarding adherence to, and effects of the protocols, were collected from the local database and the patients' hospital records. Patients' adherence to advice given pre-operatively was followed up using a study-specific questionnaire. RESULTS: The patients reported high adherence to remembered advice given. The health care professionals' adherence to the various parts of the concepts varied. ERAS® implementation resulted in more frequent gut motility stimulation (p < 0.001) and shorter duration of epidural anesthesia, site drains, and urinary catheter (p = 0.001). With prehabilitation, more patients were screened concerning nutritional status and prescribed preoperative training (p < 001). There was a significant change in weight before surgery, a shorter time to first flatus and a shorter length of stay after implementation of the concepts (p < 0.05). Complications were rare in all three groups and there were no significant differences between the groups. CONCLUSION: The implementation of an ERAS® and a prehabilitation protocol increased adherence to the protocols by both patients and healthcare professionals. An implementation of an ERAS® protocol with and without prehabilitation decreases length of stay and may decrease preoperative weight loss and time to bowel movement.

Nurturing innovative culture in a healthcare organisation - Lessons from a Swedish case study.

PURPOSE: Healthcare organisations are often described as less innovative than other organisations, since organisational culture works against innovations. In this paper, the authors ask whether it has to be that way or whether is possible to nurture an innovative culture in a healthcare organisation. The aim of this paper is to describe and analyse nurturing an innovative culture within a healthcare organisation and how culture can support innovations in such a healthcare organisation. DESIGN/METHODOLOGY/APPROACH: Based on a qualitative case study of a healthcare unit that changed, within a few years, from having no innovations to repeatedly generating innovations, the authors describe important aspects of how innovative culture can be nurtured in healthcare. Data were analysed using inductive and deductive analysis steps. FINDINGS: The study shows that it is possible to nurture an innovative culture in a healthcare organisation. Relationships and competences beyond healthcare, empowering structures and signalling the importance of innovation work with resources all proved to be important. All are aspects that a manager can influence. In this case, the manager's role in nurturing innovative culture was very important. PRACTICAL IMPLICATIONS: This study highlights that an innovative culture can be nurtured in healthcare organisations and that managers can play a key role in such a process. ORIGINALITY/VALUE: The paper describes and analyses an innovative culture in a healthcare unit and identifies important conditions and strategies for nurturing innovative culture in healthcare organisations.

PACADI: translation and adaptation of a Swedish-language version of the pancreatic cancer disease impact score.

OBJECTIVE: The Norwegian pancreatic cancer disease impact score (PACADI) is a digitalized analogue questionnaire that assesses different disease-specific symptoms. There is a need of translations of it into other languages. Therefore, the aim of this article is to describe the translation process of a Swedish version of PACADI and present its validity to EORCT QLQ PAN26. The self-administered questionnaire PACADI was translated according to guidelines and assessed by an expert panel of health care personnel. The test of its validity was performed with the disease-specific questionnaire for EORCT QLQ PAN26. Both questionnaires were completed by 66 subjects with pancreatic cancer, either before, at discharge or three months after surgery. RESULT: The results between the groups indicate that patients suffer from different symptoms at different times. The correlations between the different symptoms of the two questionnaires were fair to good. In conclusion, PACADI and QLQ PAN 26 have a good correlation and PACADI can be used in clinical practise.

Clinicians' psychological empowerment to engage in management as part of their daily work.

PURPOSE: The purpose of the article is to analyze how physicians and nurses, as the two major health care professions, experience psychological empowerment for managerial work. DESIGN/METHODOLOGY/APPROACH: The study was designed as a qualitative interview study at four primary care centers (PCCs) in Sweden. In total, 47 interviews were conducted, mainly with physicians and nurses. The first inductive analysis led us to the concept of psychological empowerment, which was used in the next deductive step of the analysis. FINDINGS: The study showed that both professions experienced self-determination for managerial work, but that nurses were more dependent on structural empowerment. Nurses experienced that they had competence for managerial work, whereas physicians were more ignorant of such competence. Nurses used managerial work to create impact on the conditions for their clinical work, whereas physicians experienced impact independently. Both nurses and physicians experienced managerial work as meaningful, but less meaningful than nurses and physicians' clinical work. PRACTICAL IMPLICATIONS: For an effective health care system, structural changes in terms of positions, roles, and responsibilities can be an important route for especially nurses' psychological empowerment. ORIGINALITY/VALUE: The qualitative method provided a complementary understanding of psychological empowerment on how psychological empowerment interacted with other factors. One such aspect was nurses' higher dependence on structural empowerment, but the most important aspect was that both physicians and nurses experienced that managerial work was less meaningful than clinical work. This implies that psychological empowerment for managerial work may only make a difference if psychological empowerment does not compete with physicians' and nurses' clinical work.

Using systems thinking to increase understanding of the innovation system of healthcare organisations.

PURPOSE: This paper applies systems thinking modelling to enhance the dynamic understanding of how to nurture an innovative culture in healthcare organisations to develop the innovation system in practice and speed up the innovative work. The model aims to provide a holistic view of a studied healthcare organisation's innovation processes, ranging from managerial values to its manifestation in improved results. DESIGN/METHODOLOGY/APPROACH: The study is based on empirical material from a healthcare unit that, within a few years, changed from having no innovations to repeatedly generating innovations. The study uses the modelling language of causal loop diagrams (CLDs) in the system dynamics methodology to identify the key important aspects found in the empirical material. FINDINGS: The proposed model, based on the stories of the interviewees, explores the dynamics of inertia when nurturing an innovative culture, identifying delays attributed to the internal change processes and system relationships. These findings underscored the need for perseverance when developing an innovative culture in the entrepreneurial phases. PRACTICAL IMPLICATIONS: The approach of using systems thinking to make empirical healthcare research results more tangible through the visual notations of CLDs and mental simulations is believed to support exploring complex phenomena to induce and nurture both individual and organisational learning. ORIGINALITY/VALUE: The results from this approach provide deepened analysis and provoke the systems view to explain how the nurturing of the culture can accelerate the innovation processes, which helps practitioners and researchers to further expand their understanding of their healthcare contexts.

If It Is Complex, Let It Be Complex - Dealing With Institutional Complexity in Hospitals Comment on "Dual Agency in Hospitals: What Strategies Do Managers and Physicians Apply to Reconcile Dilemmas Between Clinical and Economic Considerations?"

Waitzberg and colleagues identified strategies that managers and physicians in hospitals apply to reconcile dilemmas between clinical and economic considerations. Contributions that actually acknowledge the institutional complexity of hospitals and describe how to deal with it are rare. This comment explains the reason behind the institutional complexity in healthcare organizations and argues that institutional complexity is a good foundation for a well-functioning and sustainable healthcare, as long as we are able to deal with this complexity. This point underscores the importance of their contribution. However, even if the identified strategies on how to reconcile and balance different, competing demands are important, they are not easy to apply in practice. First, the strategies require frequent and high-quality interaction between different actors adhering to different institutional logics. Second, even when the strategies are applied successfully, it is difficult to make them sustainable since they rest on a fragile balance between competing logics. However, these are important avenues for future research for researchers who want to follow the route of Waitzberg and colleagues.

Neuropsychiatric Symptoms in Dementia: Considering a Clinical Role for Electroencephalography.

OBJECTIVE: Degenerative dementia is characterized by progressive cognitive decline and neuropsychiatric symptoms. People with Alzheimer's disease (AD), the most common cause of dementia, show synaptic loss and disruption of functional brain networks along with neuritic plaques and neurofibrillary tangles. Electroencephalography (EEG) directly reflects synaptic activity, and among patients with AD it is associated with slowing of background activity. The purpose of this study was to identify associations between neuropsychiatric symptoms and EEG in patients with dementia and to determine whether EEG parameters could be used for clinical assessment of pharmacological treatment of neuropsychiatric symptoms in dementia (NPSD) with galantamine or risperidone. METHODS: Seventy-two patients with EEG recordings and a score ≥10 on the Neuropsychiatric Inventory (NPI) were included. Clinical assessments included administration of the NPI, the Mini-Mental State Examination (MMSE), and the Cohen-Mansfield Agitation Inventory (CMAI). Patients underwent EEG examinations at baseline and after 12 weeks of treatment with galantamine or risperidone. EEG frequency analysis was performed. Correlations between EEG and assessment scale scores were statistically examined, as were EEG changes from baseline to the week 12 visit and the relationship with NPI, CMAI, and MMSE scores. RESULTS: Significant correlations were found between NPI agitation and delta EEG frequencies at baseline and week 12. No other consistent and significant relationships were observed between NPSD and EEG at baseline, after NPSD treatment, or in the change in EEG from baseline to follow-up. CONCLUSIONS: The limited informative findings in this study suggest that there exists a complex relationship between NPSD and EEG; hence, it is difficult to evaluate and use EEG for clinical assessment of pharmacological NPSD treatment.

Perceptions of Experiences of Recovery After Pancreaticoduodenectomy-A Phenomenographic Interview Study.

BACKGROUND: Pancreatic surgery in the context of enhanced recovery has mainly been evaluated using clinical variables. However, there is limited knowledge about patients' perceptions of recovery in this context. Hence, the aim of this study was to explore patients' perceptions of recovery after pancreatic surgery within an enhanced recovery program. OBJECTIVE: To explore the variations in patients' perceptions, a qualitatively designed study was undertaken. METHODS: Data in this phenomenographic study consisted of interviews with 19 patients at 4 to 6 weeks after surgery. RESULTS: Recovery after pancreatic surgery was classified into 5 categories, based on patients' perceptions: to be as before, affected by symptoms, physical activity, understanding the process, and facilitated by other people. CONCLUSION: The study focused on various areas of recovery, which took place between the in-hospital and after-discharge phases. Physical experiences were found to disturb recovery, in contrast to social and emotional experiences, which facilitated recovery. Variations in perceptions of recovery suggest that care may need to be more individualized, both in the preoperative and the postoperative phase. Working with realistic expectations and early patient education might better prepare patients to continue working on their own recovery after discharge from the hospital. IMPLICATIONS FOR PRACTICE: Major cancer surgery needs to be perceived as a personal journey for the patient, even in enhanced recovery program care. Preoperative education is good, but adding continuous and individually adopted education during recovery is better. Knowledge about both hindering and facilitating factors for recovery is important for the healthcare personal.

The Degradation Map Process - A Tool for Obtaining a Lean Stability Strategy in Drug Development.

Stability is fundamental when exploring a drug candidate's potential as a drug product. During the pharmaceutical industry drug development process information regarding stability and degradation are captured in different departments, e.g. from discovery to operations, and will be included in the overall control strategy. With a profound understanding of a drug candidate's degradation chemistry, a science and risk based approach in progressing a lean stability strategy is possible. This case study present a clear and visible concept to facilitate a lean stability strategy by the use of degradation maps and describes a process for how these can be used during drug development. The understanding of possible and/or observed degradation pathways will guide the design of the drug product and stability studies in development. A degradation map displays degradation pathways with short comments on the reaction/mechanism involved. The degradation map process starts with a theoretical degradation map. The map is updated as the drug project progresses, preferably after forced degradation experiments, after compatibility studies and finally when the late stage formulation is set. The degradation map should be used to capture information of intrinsic chemical properties of the active pharmaceutical ingredient (API) and can thereby be used to mitigate stability issues. The map is foremost a cross-functionally available tool collecting and visualizing stability information throughout the development process, and as such a valuable tool to efficiently develop a lean stability strategy.

Patients' perceptions of quality in Swedish primary care - a study of differences between private and public ownership.

PURPOSE: The purpose of the paper is to describe and analyze differences in patients' quality perceptions of private and public primary care centers in Sweden. DESIGN/METHODOLOGY/APPROACH: The article explores the differences in quality perceptions between patients of public and private primary care centers based on data from a large patient survey in Sweden. The survey covers seven dimensions, and in this paper the measure Overall impression was used for the comparison. With more than 80,000 valid responses, the survey covers all primary care centers in Sweden which allowed for a detailed analysis of differences in quality perceptions among patients from the different categories of owners. FINDINGS: The article contributes with a detailed description of different types of private owners: not-for-profit and for profit, as well as corporate groups and independent care centers. The results show a higher quality perception for independent centers compared to both public and corporate groups. RESEARCH LIMITATIONS/IMPLICATIONS: The small number of not-for-profit centers (21 out of 1,117 centers) does not allow for clear conclusions for this group. The results, however, indicate an even higher patient quality perception for not-for-profit centers. The study focus on describing differences in quality perceptions between the owner categories. Future research can contribute with explanations to why independent care centers receive higher patient satisfaction. SOCIAL IMPLICATIONS: The results from the study have policy implications both in a Swedish as well as international perspective. The differentiation between different types of private owners made in this paper opens up for interesting discussions on privatization of healthcare and how it affects patient satisfaction. ORIGINALITY/VALUE: The main contribution of the paper is the detailed comparison of different categories of private owners and the public owners.

Qualification of impurities based on metabolite data.

Regulatory Guidance documents ICH Q3A (R2) and ICH Q3B (R2) state that "impurities that are also significant metabolites present in animal and/or human studies are generally considered qualified". However, no guidance is provided regarding data requirements for qualification, nor is a definition of the term "significant metabolite" provided. An opportunity is provided to define those categories and potentially avoid separate toxicity studies to qualify impurities. This can reduce cost, animal use and time, and avoid delays in drug development progression. If the concentration or amount of a metabolite, in animals or human, is similar to that of the known, structurally identical impurity (arising from the administered test material), the qualification of the impurity on the grounds of it also being a metabolite is justified. We propose two complementary approaches to support conclusions to this effect: 1) demonstrate that the impurity is formed by metabolism in animals and/or man, based preferably on plasma exposures or, alternatively, amounts excreted in urine, and, where appropriate, 2) show that animal exposure to (or amount of) the impurity/metabolite is equal or greater in animals than in humans. An important factor of both assessments is the maximum theoretical concentration (or amount) (MTC or MTA) of the impurity/metabolite achievable from the administered dose and recommendations on the estimation of the MTC and MTA are presented.

EEG time signature in Alzheimer´s disease: Functional brain networks falling apart.

Spontaneous mental activity is characterized by dynamic alterations of discrete and stabile brain states called functional microstates that are thought to represent distinct steps of human information processing. Electroencephalography (EEG) directly reflects functioning of brain synapses with a uniquely high temporal resolution, necessary for investigation of brain network dynamics. Since synaptic dysfunction is an early event and best correlate of cognitive status and decline in patients along Alzheimer's disease (AD) continuum, EEG microstates might serve as valuable early markers of AD. The present study investigated differences in EEG microstate topographies and parameters (duration, occurrence and contribution) between a large cohort of healthy elderly (n = 308) and memory clinic patients: subjective cognitive decline (SCD, n = 210); mild cognitive impairment (MCI, n = 230) and AD (n = 197) and how they correlate to conventional cerebrospinal fluid (CSF) markers of AD. Four most representative microstate maps assigned as classes A, B (asymmetrical), C and D (symmetrical) were computed from the resting state EEGs since it has been shown previously that this is sufficient to explain most of the resting state EEG data. Statistically different topography of microstate maps were found between the controls and the patient groups for microstate classes A, C and D. Changes in the topography of microstate class C were associated with the CSF Aß42 levels, whereas changes in the topography of class B were linked with the CSF p-tau levels. Gradient-like increase in the contribution of asymmetrical (A and B) and gradient-like decrease in the contribution of symmetrical (C and D) maps were observed with the more severe stage of cognitive impairment. Our study demonstrated extensive relationship of resting state EEG microstates topographies and parameters with the stage of cognitive impairment and AD biomarkers. Resting state EEG microstates might therefore serve as functional markers of early disruption of neurocognitive networks in patients along AD continuum.

Degradation caused by incompatibility between sodium stearyl fumarate (PRUV) and AZD7986 in the drug product.

During compatibility study of the AZD7986 project, a peak of 3 area% at the tail (RRT 1.03) of the active pharmaceutical ingredient (API) was discovered for all tablets containing sodium stearyl fumarate (PRUV) under humid condition (e.g. 50 °C/75% RH), regardless of choice of disintegrant or filler combination. The degradant was needed to be identified to understand the corresponding reaction mechanism and help the final formulation design. Structure elucidation was therefore done by analysis using high resolution mass spectrometry. The degradant was found to be a Michael addition product of the API and fumaric acid. Reaction between deuterated fumaric acid and the API was carried to confirm the proposed structure and reaction mechanism. Fumaric acid was a degradant product of PRUV in the presence of other excipients, revealed by the stability study. The Michael addition reaction needs facilitation by water and basic conditions. The result from this study should serve as a precaution note for projects using PRUV as one of excipients where the API could act as a nucleophile. In such cases the microenvironment should be optimised to minimize the reaction, such as pH adjustment and incorporating protection from moisture.

Swedish consensus reached on recording, interpretation and reporting of neonatal continuous simplified electroencephalography that is supported by amplitude-integrated trend analysis.

Continuous monitoring of electroencephalography (EEG), with a focus on amplitude-integrated EEG (aEEG), has been used in neonatal intensive care for decades. A number of systems have been suggested for describing and quantifying aEEG patterns. Extensive full-montage EEG monitoring is used in specialised intensive care units. The American Clinical Neurophysiology Society published recommendations for defining and reporting EEG findings in critically ill adults and infants. Swedish neonatologists and clinical neurophysiologists collaborated to optimise simplified neonatal continuous aEEG and EEG recordings based on these American documents. CONCLUSION: This paper describes the Swedish consensus document produced by those meetings.

Quantitative EEG power and synchronization correlate with Alzheimer's disease CSF biomarkers.

Synaptic dysfunction is the best anatomical correlate of early cognitive impairment in Alzheimer's disease (AD). Electroencephalography (EEG) directly reflects brain electrical activity at the level of synapses. The aim of the present study was to investigate correlations of quantitative EEG measures, global field power (GFP) and global field synchronization (GFS), with conventional cerebrospinal fluid (CSF) biomarkers of neurodegeneration in patients diagnosed with subjective cognitive decline (n = 210), mild cognitive impairment (n = 230), and AD (n = 197). Decreased CSF amyloid ß42 significantly correlated with increased theta and delta GFP, whereas increased p- and t-tau with decreased alpha and beta GFP. Decreased CSF amyloid ß42 and increased p- and t-tau were significantly associated with decreased GFS alpha and beta. Subanalysis of the separate diagnostic groups demonstrated significant correlations between CSF biomarkers and generalized power and synchronization already in the subjective cognitive decline and mild cognitive impairment group. These results provide evidence that quantitative EEG measures are associated and possibly sensitive to distinct AD-like CSF biomarker profiles in cognitively impaired patients and are therefore promising early noninvasive markers of AD.

Subclinical white matter lesions and medial temporal lobe atrophy are associated with EEG slowing in a memory clinic cohort.

OBJECTIVE: The aim of the study was to describe the relationship between electroencephalographic (EEG) findings obtained by standardized visual analysis, subclinical white matter lesions (WML) and brain atrophy in a large memory clinic population. METHODS: Patients with Alzheimer's disease (AD, n=58), mild cognitive impairment (MCI, n=141), subjective cognitive impairment (SCI, n=194) had clinical, MRI based WML severity and regional atrophy assessments, and routine resting EEG recording. Background activity (BA) and episodic and continuous abnormalities were assessed visually in EEG. RESULTS: WML (p=0.006) and atrophy in medial temporal regions (MTA) (p=<0.001) were associated with slower BA in all diagnoses. WML were associated in SCI with total episodic EEG abnormalities (p=0.03). CONCLUSIONS: EEG is associated with subclinical WML burden and cortical brain atrophy in a memory clinic population. SIGNIFICANCE: Even the standard visually assessed EEG can complement a memory clinic diagnostic workup.

Healthcare quality improvement work: a professional employee perspective.

Purpose The purpose of this paper is to describe and analyze conditions that influence how employees engage in healthcare quality improvement (QI) work. Design/methodology/approach Qualitative case study based on interviews ( n=27) and observations ( n=10). Findings The main conditions that influence how employees engage in healthcare QI work are professions, work structures and working relationships. These conditions can both prevent and facilitate healthcare QI. Professions and work structures may cement existing institutional logics and thus prevent employees from engaging in healthcare QI work. However, attempts to align QI with professional logics, together with work structures that empower employees, can make these conditions increase employee engagement, which can be accomplished through positive working relationships that foster institutional work, which bridge different competing institutional logics, making it possible to overcome barriers that professions and work structures may constitute. Practical implications Understanding the conditions that influence how employees engage in healthcare QI work will make initiatives more likely to succeed. Originality/value Healthcare QI has mainly been studied from an implementer perspective, and employees have either been neglected or seen as passive resisters. Weak employee perspectives make healthcare QI research incomplete. In our research, healthcare QI work is studied closely at the actor level to understand healthcare QI from an employee perspective.

Preformulation investigation and challenges; salt formation, salt disproportionation and hepatic recirculation.

A compound, which is a selective peroxisome proliferator activated receptor (PPAR) agonist, was investigated. The aim of the presented studies was to evaluate the potential of the further development of the compound. Fundamental physicochemical properties and stability of the compound were characterized in solution by liquid chromatography and NMR and in solid-state by various techniques. The drug itself is a lipophilic acid with tendency to form aggregates in solution. The neutral form was only obtained in amorphous form with a glass-transition temperature of approximately 0°C. The intrinsic solubility at room temperature was determined to 0.03mg/mL. Chemical stability studies of the compound in aqueous solutions showed good stability for at least two weeks at room temperature, except at pH1, where a slight degradation was already observed after one day. The chemical stability in the amorphous solid-state was investigated during a period of three months. At 25°C/60% relative humidity (RH) and 40°C/75% RH no significant degradation was observed. At 80°C, however, some degradation was observed after four weeks and approximately 3% after three months. In an accelerated photostability study, degradation of approximately 4% was observed. Attempts to identify a crystalline form of the neutral compound were unsuccessful, however, salt formation with tert-butylamine, resulted in crystalline material. Results from stability tests of the presented crystalline salt form indicated improved chemical stability at conditions whereas the amorphous neutral form degraded. However, the salt form of the drug dissociated under certain conditions. The drug was administered both per oral and intravenously, as amorphous nanoparticles, to conscious dogs. Plasma profiles showed curves with secondary absorption peaks, indicating hepatic recirculation following both administration routes. A similar behavior was observed in rats after oral administration of a pH-adjusted solution. The observed double peaks in plasma exposure and the dissociation tendency of the salt form, were properties that contributed to make further development of the candidate drug challenging. Options for development of solid dosage forms of both amorphous and crystalline material of the compound are discussed.

Visual evoked potentials after hematopoietic allogeneic stem cell transplantation in childhood.

OBJECTIVE: To study visual pathway pathology detected by visual evoked potentials (VEPs) in patients treated with hematopoietic stem cell transplantation (HSCT) in childhood and to determine the impact of adverse ocular findings, somatic diseases, and conditioning regimens on the VEP results. METHODS: Ophthalmological assessments including pattern VEPs were performed in 47 of 79 patients at a median age of 15 years (range 3-21 years) in median 6 years (1-17 years) after HSCT. Somatic data were extracted from medical records. RESULTS: Eight patients of 47 (17%) demonstrated pathological VEPs with prolonged latencies bilaterally (n = 3) or unilaterally (n = 5) at their latest VEP test at an age of 12-18 years. A subnormal visual acuity was present in 8/11 eyes with pathological VEPs: one eye had cataract, six eyes had cataract surgery where of two had developed secondary cataracts. One eye had residual retinopathy of prematurity. Pathological VEPs were associated with decreased visual acuity (p = 0.00019) but not linked to gender, malignant diagnosis or conditioning. CONCLUSION: VEP recordings showed an association with decreased visual acuity but no relationship with irradiation or chemotherapy in the present study. SIGNIFICANCE: VEP recordings might be of clinical value for children with an unexplained subnormal visual acuity undergoing HSCT.