RESUMEN
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.
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Enfermedad de Alzheimer , Demencia , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Demencia/complicaciones , Demencia/diagnóstico , Demencia/tratamiento farmacológico , Electroencefalografía , Galantamina/uso terapéutico , Humanos , Pruebas Neuropsicológicas , Risperidona/uso terapéuticoRESUMEN
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.
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Contaminación de Medicamentos , Preparaciones Farmacéuticas/metabolismo , Animales , Biotransformación , Humanos , Pruebas de ToxicidadRESUMEN
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.
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Electroencefalografía/métodos , Neonatología/métodos , Neurofisiología/métodos , Humanos , Recién Nacido , SueciaRESUMEN
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.
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Empleos en Salud , Personal de Salud/psicología , Cultura Organizacional , Mejoramiento de la Calidad/organización & administración , Compromiso Laboral , Humanos , Relaciones Interprofesionales , Investigación Cualitativa , Calidad de la Atención de Salud/organización & administraciónRESUMEN
AZD9343 is a water-soluble gamma amino butyric acid (GABAB) agonist intended for symptomatic relief in gastroesophageal reflux disease (GERD) patients. The compound has good chemical stability in aqueous solutions, as well as in the solid state. Only one crystal modification has been observed to date. This polymorph is slightly hygroscopic (1.5% water uptake at 80% relative humidity (RH)), which is an improvement compared to the structurally similar agonist lesogaberan (AZD3355) which liquefies at 65% RH. Since the substance is very polar and lacks a UV chromophore, conventional separation and detection techniques cannot be used to characterize the substance and its impurities. The analytical techniques are described, focusing on the capillary electrophoresis method with indirect UV detection for assay and purity, the liquid chromatographic method for enantiomeric separation with derivatization with UV chromophore and three complementary nuclear magnetic resonance (NMR) approaches ((31)P-NMR, (13)C-NMR and (1)H-NMR) for impurities. For oral solutions, it was important to select the right concentration of phosphate buffer for the specific drug concentration and routinely use small additions of EDTA. I.V. solutions containing physiological saline as tonicity modifier could not be stored frozen at -20 °C. Properties of AZD9343 will be discussed in light of experiences from the structurally similar lesogaberan and (2R)-(3-amino-2-fluoropropyl)sulphinic acid (AFPSiA).
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Química Farmacéutica/métodos , Diseño de Fármacos , Agonistas de Receptores GABA-B/química , Ácidos Fosfínicos/química , Propanolaminas/química , Cromatografía Liquida/métodos , Cristalización , Estabilidad de Medicamentos , Electroforesis Capilar/métodos , Agonistas de Receptores GABA-B/análisis , Espectroscopía de Resonancia Magnética/métodos , Ácidos Fosfínicos/análisis , Propanolaminas/análisis , Solubilidad , Estereoisomerismo , Agua , HumectabilidadRESUMEN
BACKGROUND: The aim of the study was to describe distinct electroencephalogram (EEG) phenotypes defined after routine visual EEG analysis in a large memory clinic cohort and to investigate their relationship to cerebrospinal fluid (CSF) biomarkers. METHODS: Patients with Alzheimer's disease (n = 131), mild cognitive impairment (n = 285), subjective cognitive impairment (n = 310), and mixed dementia (n = 29) were assessed clinically with neuroimaging, EEG and CSF investigations. EEG phenotypes were based on frequency of background activity (BA) and presence and degree of episodic abnormalities (EA). RESULTS: BA and EA differed significantly (p < 0.001) between diagnostic groups. A lower CSF amyloid ß42/phospho-tau ratio and higher total tau were associated with slower BA (p < 0.01) and a higher degree of EA (p < 0.04). CONCLUSIONS: Slowing of BA in combination with EA seems to be related to biological markers of neurodegeneration.
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Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/líquido cefalorraquídeo , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico , Electroencefalografía , Fragmentos de Péptidos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Anciano , Enfermedad de Alzheimer/complicaciones , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/complicaciones , Estudios de Cohortes , Demencia/líquido cefalorraquídeo , Demencia/complicaciones , Demencia/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Trastornos de la Memoria/líquido cefalorraquídeo , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/etiología , Persona de Mediana Edad , Modelos EstadísticosRESUMEN
Lesogaberan is a potent gamma amino butyric acid agonist and has been evaluated for its utility in treatment of gastroesophageal reflux disease. Lesogaberan is a crystalline substance that absorbs considerable amounts of water above 65% relative humidity (RH) where it also liquifies. As a result of the hygroscopicity of the zwitterionic form an investigation of different salt forms was performed. Since the test compound is polar and lacks ultraviolet (UV) chromophore, conventional separation and detection techniques could not be used to characterise the test compound and the impurities. The analytical techniques are described, focusing on the capillary electrophoresis method with indirect UV detection for purity, the liquid chromatographic method for enantiomeric separation with derivatisation with UV chromophore and two complementary nuclear magnetic resonance (NMR) approaches (¹9F-NMR and ¹H-NMR) for impurities. The stability study in solution showed that solutions between pH 5 and 7 were the most stable ones, but after some time degradation occurred at room temperature. When bulk lesogaberan was stored at 25°C/60% RH no chemical degradation was observed after 1 year. At 40°C/75% RH, where the compound liquefies, a significant degradation was observed after 1 month. However, in a closed container (= 40°C) or as a napsylate salt, no degradation of lesogaberan was observed at 40°C/75% RH.
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Agonistas de Receptores de GABA-A/química , Fármacos Gastrointestinales/química , Ácidos Fosfínicos/química , Propilaminas/química , Cromatografía Líquida de Alta Presión , Contaminación de Medicamentos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Electroforesis Capilar , Agonistas de Receptores de GABA-A/análisis , Fármacos Gastrointestinales/análisis , Calor/efectos adversos , Concentración de Iones de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Espectroscopía de Resonancia Magnética , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Ácidos Fosfínicos/análisis , Difracción de Polvo , Propilaminas/análisis , Solubilidad , Espectrofotometría Ultravioleta , EstereoisomerismoRESUMEN
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.
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Atención a la Salud , Instituciones de Salud , Suecia , Investigación CualitativaRESUMEN
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.
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Procedimientos Quirúrgicos del Sistema Digestivo , Ejercicio Preoperatorio , Humanos , Procedimientos Quirúrgicos del Sistema Digestivo/efectos adversos , Tiempo de Internación , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Estudios Observacionales como AsuntoRESUMEN
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.
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Atención a la Salud , Médicos , Humanos , Instituciones de Salud , Hospitales , LógicaRESUMEN
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.
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Pancreaticoduodenectomía , Alta del Paciente , Humanos , Periodo Posoperatorio , Cuidados Preoperatorios , Investigación CualitativaRESUMEN
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.
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Desarrollo de Medicamentos , Industria Farmacéutica , Estabilidad de MedicamentosRESUMEN
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.
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Satisfacción en el Trabajo , Médicos , Humanos , Poder Psicológico , Investigación Cualitativa , SueciaRESUMEN
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.
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Instituciones de Salud , Investigación sobre Servicios de Salud , Atención a la Salud , Investigación Empírica , Análisis de SistemasRESUMEN
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.
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Lenguaje , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Psicometría , Calidad de Vida , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Suecia , Traducciones , Neoplasias PancreáticasRESUMEN
PURPOSE: This paper aims to describe the integrating and disintegrating effects of professional actions in customised care. DESIGN/METHODOLOGY/APPROACH: Using a qualitative case study, the authors examine the work practices and cultures of three Swedish child and adolescent psychiatric care units (CAP) charged with providing customised care in collaboration with other organisations. The authors conducted 62 interviews, made 11 half-day observations, and shadowed employees for two days. FINDINGS: The social embeddedness of action is crucial to understanding the professions' integrating/disintegrating activities. In the internal social context of CAP, the professions adapt to productivity-enhancing new public management (NPM) principles, resulting in integrating effects between the different professions and administrative management in the CAP units. However, CAP exercises professional dominance over the cooperating organisations. Thus, in the external social context, CAP's resistance to customised care principles exacerbates the disintegration problems among the different organisations. PRACTICAL IMPLICATIONS: The study concludes that, contrary to findings in many other studies, neither the professional logic nor NPM/customised care reforms determine the actions of professionals. In this case, the institutionalisation of some NPM methods blocks the adoption of customised care practices. ORIGINALITY/VALUE: Contrary to the widely accepted idea that resource restriction is a main source of conflict between management and the professions, the professions accept and adapt to resource restrictions, even at the expense of de-emphasising the practices of customised care. Thus, since professionals choose different operational strategies depending on the social context, the success of a normative reform measure may depend in part on its social context.
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Atención a la Salud/organización & administración , Servicios de Salud Mental/organización & administración , Atención Dirigida al Paciente/organización & administración , Rol Profesional , Adolescente , Niño , Reforma de la Atención de Salud , Humanos , Entrevistas como Asunto , SueciaRESUMEN
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.
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Propiedad , Satisfacción del Paciente , Humanos , Percepción , Atención Primaria de Salud , Calidad de la Atención de Salud , SueciaRESUMEN
Industrially produced hydroxypropyl methylcellulose (HPMC) is a chemically heterogeneous material, and it is thus difficult to predict parameters related to function on the basis of the polymer's average chemical values. In this study, the solution behavior of seven HPMC batches was correlated to the molecular weight, degree of substitution, and substituent pattern. The initial onset of phase separation, so-called clouding, generally followed an increased average molecular weight and degree of substitution. However, the slope of the clouding curve was affected by the substitution pattern, where the heterogeneously substituted batches had very shallow slopes. Further investigations showed that the appearance of a shallow slope of the clouding curve was a result of the formation of reversible polymer structures, formed as a result of the heterogeneous substituent pattern. These structures grew in size with temperature and concentration and resulted in an increase in the viscosity of the solutions at higher temperatures.
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Metilcelulosa/análogos & derivados , Derivados de la Hipromelosa , Metilcelulosa/química , Peso Molecular , Tamaño de la Partícula , Soluciones , Propiedades de Superficie , Temperatura , ViscosidadRESUMEN
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.
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Enfermedad de Alzheimer/fisiopatología , Encéfalo/fisiopatología , Disfunción Cognitiva/fisiopatología , Red Nerviosa/fisiopatología , Anciano , Anciano de 80 o más Años , Electroencefalografía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
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.