Person-centred care on the move - an interview study with programme directors in Swedish higher education.

BACKGROUND: There is an increasing trend towards person-centred care (PCC) worldwide, suggesting that PCC should be mastered by future health care professionals. This study aims to explore programme directors' views on facilitators and barriers to implementing PCC in four of the largest national study programmes in Sweden training future health care professionals. METHODS: A qualitative design was applied and interviews were conducted with 19 programme directors of Swedish national study programmes in medicine, nursing, occupational therapy and physiotherapy. The interviews were analysed using qualitative content analysis. Themes were sorted according to the Consolidated Framework for Implementation Research (CFIR) in an abductive approach. COREQ guidelines were applied. RESULTS: The overarching theme, as interpreted from the programme directors' experiences, was 'Person-centred care is on the move at different paces.' The theme relates to the domains identified by the CFIR as outer setting, innovation, inner setting and process. PCC was understood as something familiar but yet new, and the higher education institutions were in a state of understanding and adapting PCC to their own contexts. The movement in the outer setting consists of numerous stakeholders advocating for increased patient influence, which has stirred a movement in the inner setting where the higher educational institutions are trying to accommodate these new demands. Different meanings and values are ascribed to PCC, and the concept is thus also 'on the move', being adapted to traditions at each educational setting. CONCLUSION: Implementation of PCC in Swedish higher education is ongoing but fragmented and driven by individuals with a specific interest. There is uncertainty and ambiguity around the meaning and value of PCC and how to implement it. More knowledge is needed about the core of PCC as a subject for teaching and learning and also didactic strategies suitable to support students in becoming person-centred practitioners.

Is out-of-hours cholecystectomy for acute cholecystitis associated with complications?

BACKGROUND: Existing data on the safety of out-of-hours cholecystectomy are conflicting. The aim of this study was to investigate whether out-of-hours cholecystectomy for acute cholecystitis is associated with a higher risk for complications compared with surgery during office hours. METHODS: This was a population-based cohort study. The Swedish Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography Register (GallRiks) was used to investigate the association between out-of-hours cholecystectomy for acute cholecystitis and complications developing within 30 days. Data from patients who underwent cholecystectomy between 2006 and 2017 were collected. Out-of-hours surgery was defined as surgery commencing between 19.00 and 07.00 hours on weekdays, or any time at weekends (Friday 19.00 hours to Monday 07.00 hours). Multivariable logistic regression analysis was used to assess the risk of complications, with time of procedure as independent variable. The proportion of open procedures and proportion of procedures exceeding 120 min were also analysed. Adjustments were made for sex, age, ASA grade, time between admission and surgery, and hospital-specific features. RESULTS: Of 11 153 procedures included, complications occurred within 30 days in 1573 patients (14·1 per cent). The adjusted odds ratio (OR) for complications for out-of-hours versus office-hours surgery was 1·12 (95 per cent c.i. 0·99 to 1·28). The adjusted OR for procedures completed as open surgery was 1·39 (1·25 to 1·54), and that for operating time exceeding 120 min was 0·63 (0·58 to 0·69). CONCLUSION: Out-of-hours complications may relate to patient factors and the higher proportion of open procedures.

ANTECEDENTES: Los datos existentes sobre la seguridad de la colecistectomía fuera del horario laboral son discordantes. El objetivo de este estudio fue investigar si la colecistectomía para el tratamiento de la colecistitis aguda realizada fuera del horario laboral se asocia con un mayor riesgo de complicaciones en comparación con la cirugía efectuada durante el horario laboral. MÉTODOS: Se trata de un estudio de cohortes de base poblacional. Se utilizó el registro Swedish Gallstone Surgery and Endoscopic Retrograde Cholangiopancreatography Register (GallRiks) para examinar la asociación entre la colecistectomía por colecistitis aguda realizada fuera del horario laboral y las complicaciones a los 30 días. Se recogieron los datos de los pacientes en los que se realizó una colecistectomía entre 2006 y 2017. Se definió como cirugía fuera del horario laboral aquella realizada entre las 19:00 y las 07:00 de lunes a viernes y en cualquier momento durante los fines de semana (de viernes 19:00 a lunes 07:00) Se realizó un análisis de regresión logística multivariable para evaluar el riesgo de complicaciones, considerando la hora de la cirugía como variable independiente. También se analizó el porcentaje de intervenciones por vía abierta y el de aquellas cuya duración excedió de los 120 minutos. Se realizaron ajustes por sexo, edad, puntuación ASA, días desde el ingreso hasta la cirugía y características específicas del hospital. RESULTADOS: Se produjeron 1.573 (14,1%) complicaciones en las 11.153 intervenciones incluidas. La razón de oportunidades, odds ratio (OR) ajustada para las complicaciones comparando la cirugía fuera del horario laboral con la cirugía dentro del horario laboral, fue de 1,12 (i.c. del 95% 0,99-1,28). La OR ajustada para los procedimientos realizado por vía abierta fue de 1,39 (1,25-1,54). La OR ajustada para el tiempo operatorio > 120 minutos fue de 0,63 (0,58-0,69). CONCLUSIÓN: Las complicaciones que suceden en la cirugía efectuada fuera del horario laboral es más probable que se deban a factores relacionados con el paciente que con la hora del día en que se practica la cirugía. Debe tenerse en cuenta que las intervenciones realizadas por vía abierta fuera del horario laboral tienen una mayor morbilidad.

Methods to evaluate perspectives of safety, independence, activity, and participation in older persons using welfare technology. A systematic review.

Purpose: To conduct a systematic review of existing methods to evaluate the individual aspects of welfare technology from the perspectives of independence, safety, activity, and participation. Furthermore, the study aimed to describe outcomes that have been the focus of previous research to evaluate individual aspects of welfare technology in older persons living in ordinary housing. Materials and methods: A systematic literature review in PubMed, CINAHL Plus, PsycINFO, Scopus, and Web of Science. Studies selected were those that explored the use of assistive and welfare technology devices from older persons' perspectives, and which considered the concepts of independence, safety, activity and participation, and quality of life. Results: A broad spectrum of instruments was applied in the studies. For independence, three questionnaires were used in the identified studies. For safety, one instrument was used in two versions. To study activity and participation as well as quality of life, several scales were used. Additionally, several studies included qualitative approaches for evaluation, such as interviews, or posed one or more questions regarding the effects of welfare technology. Conclusions: The integration of digital assistive and welfare technology should be based on the needs of older persons, and those needs must be assessed using reliable and relevant instruments. The heterogeneity of the target group, i.e., older persons, together with the fact that assessments must give consideration to identifying goals, obstacles, and risks as well as users' preferences, implies a person-centred approach.Implications for rehabilitationThe integration of digital assistive and welfare technology should be based on older persons' needs, and those needs must be assessed using reliable and relevant instruments.The heterogeneity of the target group, i.e. older persons, together with the fact that assessments must give consideration to identifying goals, obstacles and risks as well as users' preferences, implies a person-centred approach.The ideal would be one coherent model that explores the use of digital assistive and welfare technology from the individual, economic as well as organisational dimensions. This would cover the different needs and expectations of various stakeholders, including economic and organisational, but also the needs of the older person.

Assessment of dosimetric impact of system specific geometric distortion in an MRI only based radiotherapy workflow for prostate.

Dosimetric errors in a magnetic resonance imaging (MRI) only radiotherapy workflow may be caused by system specific geometric distortion from MRI. The aim of this study was to evaluate the impact on planned dose distribution and delineated structures for prostate patients, originating from this distortion. A method was developed, in which computer tomography (CT) images were distorted using the MRI distortion field. The displacement map for an optimized MRI treatment planning sequence was measured using a dedicated phantom in a 3 T MRI system. To simulate the distortion aspects of a synthetic CT (electron density derived from MR images), the displacement map was applied to CT images, referred to as distorted CT images. A volumetric modulated arc prostate treatment plan was applied to the original CT and the distorted CT, creating a reference and a distorted CT dose distribution. By applying the inverse of the displacement map to the distorted CT dose distribution, a dose distribution in the same geometry as the original CT images was created. For 10 prostate cancer patients, the dose difference between the reference dose distribution and inverse distorted CT dose distribution was analyzed in isodose level bins. The mean magnitude of the geometric distortion was 1.97 mm for the radial distance of 200-250 mm from isocenter. The mean percentage dose differences for all isodose level bins, were ⩽0.02% and the radiotherapy structure mean volume deviations were <0.2%. The method developed can quantify the dosimetric effects of MRI system specific distortion in a prostate MRI only radiotherapy workflow, separated from dosimetric effects originating from synthetic CT generation. No clinically relevant dose difference or structure deformation was found when 3D distortion correction and high acquisition bandwidth was used. The method could be used for any MRI sequence together with any anatomy of interest.

Daily life consequences, cognitive impairment, and fatigue after transient ischemic attack.

OBJECTIVES: Studies suggest that fatigue and cognitive impairment may be present after transient ischemic attack (TIA), but little is known about consequences in daily life. The main aim was to longitudinally explore the presence of fatigue, cognitive impairment, and consequences in daily life including communication after clinically diagnosed TIA at 1 and 9 months after the event. MATERIAL AND METHODS: A consecutive sample of 46 patients (23 women, 69 ± 12.3 years) was assessed at discharge from hospital and at 1 and 9 months after TIA regarding cognition, mental fatigue, tiredness, and activities of daily life. This served as basis for an interview concerning experienced changes related to the TIA. RESULTS: Problems in daily life with probable association with the TIA were experienced by 37% (n = 45) of participants 9 months after the TIA event. Cognitive impairment was present in 40% (n = 44) after 1 month and 30% (n = 23) after 9 months. Mental fatigue was experienced by 26% (n = 42) after 1 month and 17% (n = 39) after 9 months. Communication problems were reported and increased from 7 to 14 participants between the two time points. CONCLUSIONS: A third of the TIA patients experienced problems in performance of complex activities in daily life and often communication problems within the first 9 months. Cognitive impairment and mental fatigue could be factors influencing performance in daily life and at work, but this needs to be verified in a larger sample. The risk of activity limitations indicates need for multiprofessional support and systematic routines for TIA follow-up.

Occurrence of methicillin-resistant Staphylococci in surgically treated dogs and the environment in a Swedish animal hospital.

OBJECTIVES: To investigate whether hospitalised dogs treated surgically may become culture positive for methicillin-resistant Staphylococcus pseudintermedius or methicillin-resistant Staphylococcus aureus. METHODS: Surgically treated dogs (n=45) were sampled for methicillin-resistant Staphylococcus pseudintermedius or methicillin-resistant Staphylococcus aureus on admission, before and after surgery and at the time of removal of surgical stitches. The hospital environment (n=57), including healthy dogs in the veterinary hospital environment (n=34), were sampled for methicillin-resistant Staphylococcus pseudintermedius or methicillin-resistant Staphylococcus aureus. Genetic variations among methicillin-resistant Staphylococcus pseudintermedius or methicillin-resistant Staphylococcus aureus isolates were identified through detection of restriction fragment polymorphisms. RESULTS: No dogs developed a wound infection due to methicillin-resistant Staphylococcus pseudintermedius or methicillin-resistant Staphylococcus aureus. However, there was a significant increase in the number of dogs carrying methicillin-resistant Staphylococcus pseudintermedius after hospitalisation compared to admission (P<0·001). No methicillin-resistant Staphylococcus aureus was isolated from dogs, but was present in the environment. Methicillin-resistant Staphylococcus pseudintermedius isolates were recovered from environmental surfaces and hospitalised animals, but not from healthy dogs. Methicillin-resistant Staphylococcus pseudintermedius isolates representing nine different restriction endonuclease digestion patterns were found, with two of these occurring in both the environment and on dogs. CLINICAL SIGNIFICANCE: Dogs may contract methicillin-resistant Staphylococcus pseudintermedius in association with surgery and hospitalisation. Resistant bacteria may be transmitted between dogs, staff and the environment. Dogs colonised with methicillin-resistant Staphylococcus pseudintermedius may be a source for hospital- and community-acquired infections.

Sequence analysis of human rhinovirus aspirated from the nasopharynx of patients with relapsing-remitting MS.

BACKGROUND: Upper respiratory infections were reported to trigger multiple sclerosis relapses. A relationship between picornavirus infections and MS relapses was recently reported. OBJECTIVE: To evaluate whether human rhinovirus is associated with multiple sclerosis relapses and whether any particular strain is predominant. METHOD: Nasopharyngeal fluid was aspirated from 36 multiple sclerosis patients at pre-defined critical time points. Reverse-transcriptase-PCR was performed to detect human rhinovirus-RNA. Positive amplicons were sequenced. RESULTS: We found that rhinovirus RNA was present in 17/40 (43%) of specimens obtained at the onset of a URTI in 19 patients, in 1/21 specimens during convalescence after URTI in 14 patients, in 0/6 specimens obtained in 5 patients on average a week after the onset of an "at risk" relapse, occurring within a window in time from one week before to three weeks after an infection, and in 0/17 specimens obtained after the onset of a "not at risk" relapse not associated with any infection in 12 patients. Fifteen specimens from healthy control persons not associated with URTI were negative. The frequency of HRV presence in URTI was similar to that reported for community infections. Eight amplicons from patients represented 5 different HRV strains. CONCLUSION: We were unable to reproduce previous findings of association between HRV infections and multiple sclerosis relapses. HRV was not present in nasopharyngeal aspirates obtained during "at risk" or "not at risk" relapses. Sequencing of HRV obtained from patients during URTI did not reveal any strain with predominance in multiple sclerosis.

Cytokine secretion in decidual mononuclear cells from term human pregnancy with or without labour: ELISPOT detection of IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha.

Cytokines are believed to be important in maintaining pregnancy and in the process of labour induction in humans. The aim of this study was to investigate the secretion of the cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-10, transforming growth factor-beta (TGF-beta) and tumour necrosis factor-alpha (TNF-alpha) in decidual tissue with or without labour. Decidual tissue was collected from 32 healthy women undergoing elective caesarean sections before the onset of labour (n=17) or after normal vaginal delivery (n=15). Mononuclear cells were analysed for cytokine secretion with ELISPOT. To validate the widely used method of tissue collected at caesarean sections and after vaginal deliveries as a representative of before and after labour, respectively, placenta biopsies were collected from 12 healthy women to study the expression of the prostaglandin pathway enzymes cyclooxygenase-2 (COX-2) and microsomal prostaglandin E(2) synthase (mPGES). Decidual mononuclear cells from term human pregnancy spontaneously secrete IFN-gamma, IL-4, IL-10, TGF-beta and TNF-alpha. No difference was seen in cytokine secretion with or without labour, indicating that decidual leukocytes are not the main cell population responsible for plausible cytokine regulation in the process of termination of pregnancy. Placental tissues obtained after vaginal delivery showed a higher mRNA expression of the prostaglandin regulating molecules COX-2 and mPGES than tissues from caesarean sections before the onset of labour, validating that the model can be used as a representative of the state before and after labour.

Psychometric evaluation of a Swedish version of the Reiss Screen for Maladaptive Behavior.

BACKGROUND: People with intellectual disability (ID) are afflicted by mental health problems to a greater extent than other individuals, and the coexistence of ID and mental health problems involves diagnostic as well as treatment difficulties. METHODS: A Swedish version of the Reiss Screen for Maladaptive Behavior (RSMB), an instrument used for identification of mental health problems in people with intellectual disability (ID) was evaluated in terms of inter-rater agreement, internal consistency, item grouping and criterion validity based on a random sample and a clinical group of adults with ID. RESULTS: The Swedish version of the RSMB had moderate-to-low inter-rater agreement on specific items and good internal consistency. The total score was considered to be a fairly reliable measure of a positive or negative result on the RSMB. A principal component analysis yielded seven interpretable components. A close resemblance in sets of items between the Swedish version and the original version of RSMB was found for three subscales: Aggressive Behaviour, Avoidance Disorder and Depression (Behavioural Signs). The outcome of the criterion validity analysis indicated a higher rate of false negatives than false positives. CONCLUSIONS: The potential influence of concurrent psychopharmacological treatment is discussed. It is concluded that the Swedish version of the RSMB can be used as intended by staff as a primary screening device for the identification of mental health problems among people with ID in a Swedish setting.

Exploration of sequence space for protein engineering.

The process of protein engineering is currently evolving towards a heuristic understanding of the sequence-function relationship. Improved DNA sequencing capacity, efficient protein function characterization and improved quality of data points in conjunction with well-established statistical tools from other industries are changing the protein engineering field. Algorithms capturing the heuristic sequence-function relationships will have a drastic impact on the field of protein engineering. In this review, several alternative approaches to quantitatively assess sequence space are discussed and the relatively few examples of wet-lab validation of statistical sequence-function characterization/correlation are described.

Analysis of Schizosaccharomyces pombe mediator reveals a set of essential subunits conserved between yeast and metazoan cells.

With the identification of eight new polypeptides, we here complete the subunit characterization of the Schizosaccharomyces pombe RNA polymerase II holoenzyme. The complex contains homologs to all 10 essential gene products present in the Saccharomyces cerevisiae Mediator, but lacks clear homologs to any of the 10 S. cerevisiae components encoded by nonessential genes. S. pombe Mediator instead contains three unique components (Pmc2, -3, and -6), which lack homologs in other cell types. Presently, pmc2(+) and pmc3(+) have been shown to be nonessential genes. The data suggest that S. pombe and S. cerevisiae share an essential protein module, which associates with nonessential speciesspecific subunits. In support of this view, sequence analysis of the conserved yeast Mediator components Med4 and Med8 reveals sequence homology to the metazoan Mediator components Trap36 and Arc32. Therefore, 8 of 10 essential genes conserved between S. pombe and S. cerevisiae also have a metazoan homolog, indicating that an evolutionary conserved Mediator core is present in all eukaryotic cells. Our data suggest a closer functional relationship between yeast and metazoan Mediator than previously anticipated.

Mediator--a universal complex in transcriptional regulation.

The Mediator complex is essential for basal and regulated expression of nearly all RNA polymerase II-dependent genes in the Saccharomyces cerevisiae genome. Mediator acts as a bridge, conveying regulatory information from enhancers and other control elements to the promoter. It is now clear that Mediator-like complexes also exist in higher eukaryotic cells and that they have an important role in metazoan transcriptional regulation. However, the exact mechanism of Mediator-dependent transcriptional regulation remains unclear. We review here some recent advances in our understanding of Mediator structure and function. We also discuss a model to account for the functional and evolutionary relationship between yeast and metazoan Mediators. As an appendix to this review, we have created a database, MEDB, in which we have compiled information about all the S. cerevisiae Mediator subunits and their homologues in other eukaryotic cells (http://bio.lundberg.gu.se/medb/).

Increased in vivo apoptosis in cells lacking mitochondrial DNA gene expression.

We have attempted to determine whether loss of mtDNA and respiratory chain function result in apoptosis in vivo. Apoptosis was studied in embryos with homozygous disruption of the mitochondrial transcription factor A gene (Tfam) and tissue-specific Tfam knockout animals with severe respiratory chain deficiency in the heart. We found massive apoptosis in Tfam knockout embryos at embryonic day (E) 9.5 and increased apoptosis in the heart of the tissue-specific Tfam knockouts. Furthermore, mtDNA-less (rho(0)) cell lines were susceptible to apoptosis induced by different stimuli in vitro. The data presented here provide in vivo evidence that respiratory chain deficiency predisposes cells to apoptosis, contrary to previous assumptions based on in vitro studies of cultured cells. These results suggest that increased apoptosis is a pathogenic event in human mtDNA mutation disorders. The finding that respiratory chain deficiency is associated with increased in vivo apoptosis may have important therapeutic implications for human disease. Respiratory chain deficiency and cell loss and/or apoptosis have been associated with neurodegeneration, heart failure, diabetes mellitus, and aging. Furthermore, chemotherapy and radiation treatment of cancer are intended to induce apoptosis in tumor cells. It would therefore be of interest to determine whether manipulation of respiratory chain function can be used to inhibit or enhance apoptosis in these conditions.

Reliability and responsiveness of three different pain assessments.

The visual analogue scale (VAS) and ordered categorical scales, i.e. numeric rating scales (NRS), are commonly used in the assessment of pain. However, these scales are bounded by fixed endpoints and thus the range of measurement is limited. The disparity in repeated assessments of perceived pain intensity with the VAS, NRS, and electrical stimulation applied as a matching stimulus was studied in 69 patients (48 women and 21 men, 19-72 years) with chronic nociceptive or neurogenic pain. Responsiveness with transcutaneous electrical nerve stimulation (TENS) using the same measurement procedures was evaluated in the same patients. Comparison of results from the three pain assessments showed that the painmatcher is at least as reliable and responsive as VAS and NRS. None of the three measurements showed evidence for systematic disagreement and had only significant random individual disagreement. They also showed evidence for responsiveness.

Structural organization of yeast and mammalian mediator complexes.

Structures of yeast Mediator complex, of a related complex from mouse cells and of thyroid hormone receptor-associated protein complex from human cells have been determined by three-dimensional reconstruction from electron micrographs of single particles. All three complexes show a division in two parts, a "head" domain and a combined "middle-tail" domain. The head domains of the three complexes appear most similar and interact most closely with RNA polymerase II. The middle-tail domains show the greatest structural divergence and, in the case of the tail domain, may not interact with polymerase at all. Consistent with this structural divergence, analysis of a yeast Mediator mutant localizes subunits that are not conserved between yeast and mammalian cells to the tail domain. Biochemically defined Rgr1 and Srb4 modules of yeast Mediator are then assigned to the middle and head domains.

Directed evolution: the 'rational' basis for 'irrational' design.

The development of powerful genetic manipulation formats has revolutionized the creation of functional biological molecules. Recent advances in directed evolution demonstrate that multiple properties of proteins can be optimized simultaneously and rapidly. Improved proteins often contain multiple and dispersed substitutions that act synergistically to improve enzyme properties and function. The benefits of such multiple changes are often not predictable from a priori structural knowledge. Furthermore, alternative solutions to gaining functional change can be obtained.

Mediator-nucleosome interaction.

Mediator, a multiprotein complex involved in the regulation of RNA polymerase II transcription, binds to nucleosomes and acetylates histones. Three lines of evidence identify the Nut1 subunit of Mediator as responsible for the histone acetyltransferase (HAT) activity. An "in-gel" HAT assay reveals a single band of the appropriate size. Sequence alignment shows significant similarity of Nut1 to the GCN5-related N-acetyltransferase superfamily. Finally, recombinant Nut1 exhibits HAT activity in an in-gel assay.

Subunit interactions in yeast transcription/repair factor TFIIH. Requirement for Tfb3 subunit in nucleotide excision repair.

A yeast strain harboring a temperature-sensitive allele of TFB3 (tfb3(ts)), the 38-kDa subunit of the RNA polymerase II transcription/nucleotide excision repair factor TFIIH, was found to be sensitive to ultraviolet (UV) radiation and defective for nucleotide excision repair in vitro. Interestingly, tfb3(ts) failed to grow on medium containing caffeine. A comprehensive pairwise two-hybrid analysis between yeast TFIIH subunits identified novel interactions between Rad3 and Tfb3, Tfb4 and Ssl1, as well as Ssl2 and Tfb2. These interactions have facilitated a more complete model of the structure of TFIIH and the nucleotide excision repairosome.

Purification and characterization of RNA polymerase II holoenzyme from Schizosaccharomyces pombe.

We have purified the RNA polymerase II holoenzyme from Schizosaccharomyces pombe to near homogeneity. The Mediator complex is considerably smaller than its counterpart in Saccharomyces cerevisiae, containing only nine polypeptides larger than 19 kDa. Five of these Mediator subunits have been identified as the S. pombe homologs to Rgr1, Srb4, Med7, and Nut2 found in S. cerevisiae and the gene product of a previously uncharacterized open reading frame, PMC2, with no clear homologies to any described protein. The presence of Mediator in a S. pombe RNA polymerase II holoenzyme stimulated phosphorylation of the C-terminal domain by TFIIH purified from S. pombe. This stimulation was species-specific, because S. pombe Mediator could not stimulate TFIIH purified from S. cerevisiae. We suggest that the overall structure and mechanism of the Mediator is evolutionary conserved. The subunit composition, however, has evolved to respond properly to physiological signals.