The presence of a CD4(+) CD25(high) CD45RO(+) CD127(high) T cell population correlates with the clinical status of kidney transplant recipients

Introduction: Recent data have suggested that a population of CD4+ CD25high T cells, phenotypically characterized by the expression of CD45RO and CD127, is significantly expanded in stable liver and kidney transplant recipients and represents alloreactive T cells. We analyzed this putative new alloreactive cellular marker in various groups of kidney transplant recipients. Patients & methods: Flow cytometry was used to analyze the expression of CD25, CD45RO and CD127 on peripheral CD4+ T cells. Of 73 kidney transplant recipients, 59 had a stable graft function under standard immunosuppressive therapy (IS), 5 had biopsy-proven chronic humoral rejection (CHR), 8 were stable under minimal IS and one was an operationally "tolerant" patient who had discontinued IS for more than 3 years. Sixty-six healthy subjects (HS) were studied as controls. Results: Overall, the alloreactive T cell population was found to be significantly increased in the 73 kidney recipients (mean ± SE: 15.03 ± 1.04% of CD4+ CD25high T cells) compared to HS (5.93 ± 0.39%) (p<0.001). In the 5 patients with CHR, this population was highly expanded (31.33 ± 4.16%), whereas it was comparable to HS in the 8 stable recipients receiving minimal IS (6.12 ± 0.86%), in 4 patients who had been switched to sirolimus (4.21 ± 0.53%) as well as in the unique "tolerant" recipient (4.69%). Intermediate levels (15.84 ± 0.93%) were found in the 55 recipients with stable graft function on standard CNI-based IS. Regulatory T cells, defined as CD4+CD25high FoxP3+ CD127low, were found to be significantly reduced in all recipients except in those with minimal or no IS, and this reduction was particularly striking in recipients with CHR. Conclusion: After kidney transplantation, an alloreactive T cell population was found to be significantly expanded and it correlates with the clinical status of the recipients. Interestingly, in stable patients with minimal (or no) IS as well as in patients on sirolimus, alloreactive T cells were comparable the healthy controls. Measuring circulating CD4+CD25high CD45RO+ CD127high T cells may become a useful monitoring tool after transplantation.

Du delirium au syndrome démentiel: prise en charge médicamenteuse dans les EMS fribourgeois [Management of elderly patients with delirium or dementia in Swiss nursing homes].

Management of elderly patients with delirium or dementia in Swiss nursing homes Dementia and delirium are among the most frequent medical conditions in older nursing home residents. Their management require a coordinated interdisciplinary approach, including for drug prescription. Using a systematic literature review of published meta-analyses and guidelines, prescription algorithms were developed adressing the pharmacological management of cognitive symptoms of dementia and delirium in older nursing home residents in the canton of Fribourg.

Web Presence Building and Performance Measuring in Business-to-Business Markets

Tutkimuksen tavoite oli selvittää yrityksen web toiminnan rakentamisen vaiheita sekä menestyksen mittaamista. Rakennusprosessia tutkittiin viisiportaisen askelmallin avulla. Mallin askeleet ovat; arviointi, strategian muotoilu, suunnitelma, pohjapiirros ja toteutus. Arviointi- ja toteutusvaiheiden täydentämiseksi sekä erityisesti myös internet toiminnan onnistumisen mittaamisen avuksi internet toiminnan hyödyt (CRM,kommunikointi-, myynti-, ja jakelukanava hyödyt markkinoinnin kannalta) käsiteltiin. Toiminnan menestyksen arvioinnin avuksi esiteltiin myös porrasmalli internet toimintaan. Porrasmalli määrittelee kauppakulissi-, dynaaminen-, transaktio- ja e-businessportaat. Tutkimuksessa löydettiin menestystekijöitä internet toimintojen menestykselle. Nämä tekijät ovat laadukas sisältö, kiinnostavuus, viihdyttävyys, informatiivisuus, ajankohtaisuus, personoitavuus, luottamus, interaktiivisuus, käytettävyys, kätevyys, lojaalisuus, suoriutuminen, responssiivisuus ja käyttäjätiedon kerääminen. Mittarit jaettiin tutkimuksessa aktiivisuus-, käyttäytymis- ja muunnosmittareihin. Lisäksi muita mittareita ja menestysindikaattoreita esiteltiin. Nämä menestyksen elementit ja mittarit koottiin yhteen uudessa internet toimintojen menestyksenarviointimallissa. Tutkielman empiirisessä osuudessa,esitettyjä teorioita peilattiin ABB:n (ABB:n sisällä erityisesti ABB Stotz-Kontakt) web toimintaan. Apuna olivat dokumenttianalyysi sekä haastattelut. Empiirinen osa havainnollisti teoriat käytännössä ja toi ilmi mahdollisuuden teorioiden laajentamiseen. Internet toimintojen rakentamismallia voidaan käyttää myös web toimintojen kehittämiseen ja porrasmalli sopii myös nykyisten internet toimintojen arvioimiseen. Mittareiden soveltaminen käytännössä toi kuitenkin ilmi tarpeen niiden kehittämiseen ja aiheen lisätutkimukseen. Niiden tulisi olla myös aiempaatiiviimmin liitetty kokonaisvaltaisen liiketoiminnan menestyksen mittaamiseen.

Validation of the spiritual distress assessment tool in older hospitalized patients.

ABSTRACT:¦BACKGROUND: The Spiritual Distress Assessment Tool (SDAT) is a 5-item instrument developed to assess unmet spiritual needs in hospitalized elderly patients and to determine the presence of spiritual distress. The objective of this study was to investigate the SDAT psychometric properties.¦METHODS: This cross-sectional study was performed in a Geriatric Rehabilitation Unit. Patients (N = 203), aged 65 years and over with Mini Mental State Exam score ≥ 20, were consecutively enrolled over a 6-month period. Data on health, functional, cognitive, affective and spiritual status were collected upon admission. Interviews using the SDAT (score from 0 to 15, higher scores indicating higher distress) were conducted by a trained chaplain. Factor analysis, measures of internal consistency (inter-item and item-to-total correlations, Cronbach α), and reliability (intra-rater and inter-rater) were performed. Criterion-related validity was assessed using the Functional Assessment of Chronic Illness Therapy-Spiritual well-being (FACIT-Sp) and the question "Are you at peace?" as criterion-standard. Concurrent and predictive validity were assessed using the Geriatric Depression Scale (GDS), occurrence of a family meeting, hospital length of stay (LOS) and destination at discharge.¦RESULTS: SDAT scores ranged from 1 to 11 (mean 5.6 ± 2.4). Overall, 65.0% (132/203) of the patients reported some spiritual distress on SDAT total score and 22.2% (45/203) reported at least one severe unmet spiritual need. A two-factor solution explained 60% of the variance. Inter-item correlations ranged from 0.11 to 0.41 (eight out of ten with P < 0.05). Item-to-total correlations ranged from 0.57 to 0.66 (all P < 0.001). Cronbach α was acceptable (0.60). Intra-rater and inter-rater reliabilities were high (Intraclass Correlation Coefficients ranging from 0.87 to 0.96). SDAT correlated significantly with the FACIT-Sp, "Are you at peace?", GDS (Rho -0.45, -0.33, and 0.43, respectively, all P < .001), and LOS (Rho 0.15, P = .03). Compared with patients showing no severely unmet spiritual need, patients with at least one severe unmet spiritual need had higher odds of occurrence of a family meeting (adjOR 4.7, 95%CI 1.4-16.3, P = .02) and were more often discharged to a nursing home (13.3% vs 3.8%; P = .027).¦CONCLUSIONS: SDAT has acceptable psychometrics properties and appears to be a valid and reliable instrument to assess spiritual distress in elderly hospitalized patients.

Cognition et psychopathologie chez les nonagénaires et centenaires vivant en établisement médico-social gériatrique en Suisse : focalisation sur l'anosognosie = [Cognition and psychopathology in nonagenarians and centenarians living in geriatric nursing homes in Switzerland : a focus on anosognosia]

Les nonagénaires et centenaires voient actuellement leur nombre augmenter considérablement, beaucoup d'entre eux vivant en maison de retraite. Pour cette population, on dispose de très peu de données au sujet de la Symptomatologie psychiatrique et des capacités cognitives autres que mnésiques. Cette étude exploratoire se concentre sur l'anosognosie et ses liens avec les symptômes psychiatriques et cognitifs courants. Cinquante-huit sujets âgés de 90 ans ou plus ont été recrutés dans des établissements médico-sociaux gériatriques et divisés en 5 groupes selon le Mini Mental State Examination (MMSE). Les évaluations incluent le test des 5 mots, le CLOX, les fluences lexicales et catégorielles, le questionnaire d'anosognosie- démence (AQ-D), l'inventaire neuropsychiatrique (NPI) et l'index de comorbidité de Charlson. Les sujets étudiés présentent une atteinte cognitive modérée, le MMSE moyen (±DS) étant à 15.41 ± 7.04. L'anosognosie augmente avec l'atteinte cognitive, étant associée avec tous les domaines cognitifs, mais aussi avec les symptômes psychopathologiques d'apathie et d'agitation. Les sujets ayant une atteinte cognitive légère semblent moins anosognosiques que ceux avec l'atteinte cognitive la plus faible ou ceux ne présentant aucune atteinte. Ni l'anosognosie ni les symptômes psychopathologiques ne sont liés aux comorbidités somatiques. Chez les résidents très âgés étudiés vivant en maison de retraite, l'anosognosie est principalement légère. Elle est associée à des changements cognitifs, mais aussi psychopathologiques. Des investigations supplémentaires sont toutefois nécessaires pour déterminer s'il existe un lien causal entre l'anosognosie et les atteintes psychopathologiques.

Study of the incorporation and the anti-tumour efficacy of radio-iododeoxyuridine according to the cellular cycle and in presence of synthesis inhibitor of thymidine

Résumé La iododeoxyuridine (IdUrd), une fois marqué au 123I ou au 125I, est un agent potentiel pour des thérapies par rayonnements Auger. Cependant, des limitations restreignent son incorporation dans l'ADN. Afin d'augmenter celle-ci, différents groupes ont étudié la fluorodeoxyuridine (FdUrd), qui favorise l'incorporation d'analogue de la thymidine, sans toutefois parvenir à une toxicité associé plus importante. Dans notre approche, 3 lignées cellulaires de glioblastomes humains et une lignée de cancer ovarien ont été utilisées. Nous avons observé, 16 à 24 h après un court pré-traitement à la FdUrd, un fort pourcentage de cellules s'accumulant en phase S. Plus qu'une accumulation, c'était une synchronisation des cellules, celles-ci restant capables d'incorporer la radio-IdIrd et repartant dans le cycle cellulaire. De plus, ces cellules accumulées après un pré-traitement à la FdUrd étaient plus radio-sensibles. Après le même intervalle de 16 à 24 h suivant la FdUrd, les 4 lignées cellulaires ont incorporé des taux plus élevés de radio-IdUrd que sans ce prétraitement. Une corrélation temporelle entre l'accumulation des cellules en phase S et la forte incorporation de radio-IdUrd a ainsi été révélée 16 à 24 h après pré-traitement à la FdUrd. Les expériences de traitement par rayonnements Auger sur les cellules accumulées en phase S ont montré une augmentation significative de l'efficacité thérapeutique de 125I-IdUrd comparé aux cellules non prétraitées à la FdUrd. Une première estimation a permis de déterminer que 100 désintégrations de 125I par cellules étant nécessaires afin d'atteindre l'efficacité thérapeutique. De plus, p53 semble jouer un rôle dans l'induction directe de mort cellulaire après des traitements par rayonnements Auger, comme indiqué par les mesures par FACS d'apoptose et de nécrose 24 et 48 h après le traitement. Concernant les expériences in vivo, nous avons observé une incorporation marquée de la radio-IdUrd dans l'ADN après un pré-traitement à la FdUrd dans un model de carcinomatose ovarienne péritonéale. Une augmentation encore plus importante a été observée après injection intra-tumorale dans des transplants sous-cutanés de glioblastomes sur des souris nues. Ces modèles pourraient être utilisés pour de plus amples études de diffusion de radio-IdUrd et de thérapie par rayonnement Auger. En conclusion, ce travail montre une première application réussie de la FdUrd afin d'accroître l'efficacité de la radio-IdUrd par traitements aux rayonnements Auger. La synchronisation des cellules en phase S combinée avec la forte incorporation de radio-IdUrd dans l'ADN différées après un pré-traitement à la FdUrd ont montré le gain thérapeutique attendu in vitro. De plus, des études in vivo sont tout indiquées après les observations encourageantes d'incorporation de radio-IdUrd dans les models de transplants sous-cutanés de glioblastomes et de tumeurs péritonéales ovariennes. Summary Iododeoxyuridine (IdUrd), labelled with 123I or 125I, could be a potential Auger radiation therapy agent. However, limitations restrict its DNA incorporation in proliferating cells. Therefore, fluorodeoxyuridine (FdUrd), which favours incorporation of thymidine analogues, has been studied by different groups in order to increase radio-IdUrd DNA incorporation, however therapeutic efficacy increase could not be reached. In our approach, 3 human glioblastoma cell lines with different p53 expression and one ovarian cancer line were pre-treated with various FdUrd conditions. We observed a high percentage of cells accumulating in early S phase 16 to 24 h after a short and non-toxic FdUrd pre-treatment. More than an accumulation, this was a synchronization, cells remaining able to incorporate radio-IdUrd and re-entering the cell cycle. Furthermore, the S phase accumulated cells post FdUrd pre-treatment were more radiosensitive. After the same delay of 16 to 24 h post FdUrd pre-treatment, the 4 cell lines were incorporating higher rates of radio-IdUrd compared with untreated cells. A time correlation between S phase accumulation and high radio-IdUrd incorporation was therefore revealed 16 to 24 h post FdUrd pre-treatment. Auger radiation treatment experiments performed on S phase enriched cells showed a significant increase of killing efficacy of 125I-IdUrd compared with cells not pre-treated with FdUrd. A first estimation indicates further that about 100 125I decays were required to reach killing in the targeted cells. Moreover, p53 might play a role on the direct induction of cell death pathways after Auger radiation treatments, as indicated by differential apoptosis and necrosis induction measured by FACS 24 and 48 h after treatment initiation. Concerning in vivo results, we observed a marked DNA incorporation increase of radio-IdUrd after FdUrd pre-treatment in peritoneal carcinomatosis in SCID mice. Even higher incorporation increase was observed after intra-tumoural injection of radio-IdUrd in subcutaneous glioblastoma transplants in nude mice. These tumour models might be further useful for diffusion of radio-IdUrd and Auger radiation therapy studies. In conclusion, these data show a first successful application of thymidine synthesis inhibition able to increase the efficacy of radio-IdUrd Auger radiation treatment. The S phase synchronization combined with a high percentage DNA incorporation of radio-IdUrd delayed post FdUrd pre-treatment provided the expected therapeutic gain in vitro. Further in vivo studies are indicated after the observations of encouraging radio-IdUrd uptake experiments in glioblastoma subcutaneous xenografts and in an ovarian peritoneal carcinomatosis model.

Can eukaryotic cells monitor the presence of unreplicated DNA?

Completion of DNA replication before mitosis is essential for genome stability and cell viability. Cellular controls called checkpoints act as surveillance mechanisms capable of detecting errors and blocking cell cycle progression to allow time for those errors to be corrected. An important question in the cell cycle field is whether eukaryotic cells possess mechanisms that monitor ongoing DNA replication and make sure that all chromosomes are fully replicated before entering mitosis, that is whether a replication-completion checkpoint exists. From recent studies with smc5–smc6 mutants it appears that yeast cells can enter anaphase without noticing that replication in the ribosomal DNA array was unfinished. smc5–smc6 mutants are proficient in all known cellular checkpoints, namely the S phase checkpoint, DNA-damage checkpoint, and spindle checkpoint, thus suggesting that none of these checkpoints can monitor the presence of unreplicated segments or the unhindered progression of forks in rDNA. Therefore, these results strongly suggest that normal yeast cells do not contain a DNA replication-completion checkpoint.

Increasing prehospital emergency medical service interventions for nursing home residents.

QUESTION: In the ageing European population, the proportion of interventions by the emergency medical services (EMS) for elderly patients is increasing, but little is known about the recent trend of EMS interventions in nursing homes. The aim of this analysis was to describe the evolution of the incidence of requests for prehospital EMS interventions for nursing home residents aged 65 years and over between 2004 and 2013. METHODS: A prospective population-based register of routinely collected data for each EMS intervention in the Canton of Vaud. Linear time trends of incidence of requests to the EMS in nursing homes were calculated and stratified by age categories. RESULTS: The number of ambulance interventions in nursing homes for people aged 65 years and over (65+) increased by 68.9% (1124‒1898) between 2004 and 2013. A significant linear increase of the annual incidence of requests to EMS per 1,000 nursing home residents was found for people aged 65-79 (10.2, 95% confidence interval [CI] 6.2-14.2), 80-89 (16.5, 95% CI 14.0-19.0) and over 90 (12.1, 95% CI 5.8-18.4). EMS interventions in nursing home residents who required an emergency physician increased during the same period by 205.6% (from 106 to 324), representing an increase from 2% to 7% of all emergency physician interventions in the Canton. CONCLUSIONS: Our results confirmed an important increase in the incidence of EMS interventions in nursing homes during the last decade, far exceeding the actual increase of the nursing home population during the same period. This evolution represents an important opportunity to reconsider the EMS missions in the context of an ageing society.

Assessment of inflammatory Bowel Disease patient's needs and problems from a nursing perspective

BACKGROUND: In this study, we aimed at assessing Inflammatory Bowel Disease patients' needs and current nursing practice to investigate to what extent consensus statements (European Crohn's and Colitis Organization) on the nursing roles in caring for patients with IBD concur with local practice. METHODS: We used a mixed-method convergent design to combine quantitative data prospectively collected in the Swiss IBD cohort study and qualitative data from structured interviews with IBD healthcare experts. Symptoms, quality of life, and anxiety and depression scores were retrieved from physician charts and patient self-reported questionnaires. Descriptive analyses were performed based on quantitative and qualitative data. RESULTS: 230 patients of a single center were included, 60% of patients were males, and median age was 40 (range 18-85). The prevalence of abdominal pain was 42%. Self-reported data were obtained from 75 out of 230 patients. General health was perceived significantly lower compared with the general population (p < 0.001). Prevalence of tiredness was 73%; sleep problems, 78%; issues related to work, 20%; sexual constraints, 35%; diarrhea, 67%; being afraid of not finding a bathroom, 42%; depression, 11%; and anxiety symptoms, 23%. According to experts' interviews, the consensus statements are found mostly relevant with many recommendations that are not yet realized in clinical practice. CONCLUSION: Identified prevalence may help clinicians in detecting patients at risk and improve patient management. © 2015 S. Karger AG, Basel.

Nursing student-patient relationship and associated factors

The purpose of this study was to analyse the nursing student-patient relationship and factors associated with this relationship from the point of view of both students and patients, and to identify factors that predict the type of relationship. The ultimate goal is to improve supervised clinical practicum with a view to supporting students in their reciprocal collaborative relationships with patients, increase their preparedness to meet patients’ health needs, and thus to enhance the quality of patient care. The study was divided into two phases. In the first phase (1999-2005), a literature review concerning the student-patient relationship was conducted (n=104 articles) and semi-structured interviews carried out with nursing students (n=30) and internal medicine patients (n=30). Data analysis was by means of qualitative content analysis and Student-Patient Relationship Scales, which were specially developed for this research. In the second phase (2005-2007), the data were collected by SPR scales among nursing students (n=290) and internal medicine patients (n=242). The data were analysed statistically by SPSS 12.0 software. The results revealed three types of student-patient relationship: a mechanistic relationship focusing on the student’s learning needs; an authoritative relationship focusing on what the student assumes is in the patient’s best interest; and a facilitative relationship focusing on the common good of both student and patient. Students viewed their relationship with patients more often as facilitative and authoritative than mechanistic, while in patients’ assessments the authoritative relationship occurred most frequently and the facilitative relationship least frequently. Furthermore, students’ and patients’ views on their relationships differed significantly. A number of background factors, contextual factors and consequences of the relationship were found to be associated with the type of relationship. In the student data, factors that predicted the type of relationship were age, current year of study and support received in the relationship with patient. The higher the student’s age, the more likely the relationship with the patient was facilitative. Fourth year studies and the support of a person other than a supervisor were significantly associated with an authoritative relationship. Among patients, several factors were found to predict the type of nursing student-patient relationships. Significant factors associated with a facilitative relationship were university-level education, several previous hospitalizations, admission to hospital for a medical problem, experience of caring for an ill family member and patient’s positive perception of atmosphere during collaboration and of student’s personal and professional growth. In patients, positive perceptions of student’s personal and professional attributes and patient’s improved health and a greater commitment to self-care, on the other hand, were significantly associated with an authoritative relationship, whereas positive perceptions of one’s own attributes as a patient were significantly associated with a mechanistic relationship. It is recommended that further research on the student-patient relationship and related factors should focus on questions of content, methodology and education.

Effect Estimation of an Innovative Nursing Intervention to Improve Delirium among Home-Dwelling Older Adults: A Randomized Controlled Pilot Trial.

AIMS: Estimating the effect of a nursing intervention in home-dwelling older adults on the occurrence and course of delirium and concomitant cognitive and functional impairment. METHODS: A randomized clinical pilot trial using a before/after design was conducted with older patients discharged from hospital who had a medical prescription to receive home care. A total of 51 patients were randomized into the experimental group (EG) and 52 patients into the control group (CG). Besides usual home care, nursing interventions were offered by a geriatric nurse specialist to the EG at 48 h, 72 h, 7 days, 14 days, and 21 days after discharge. All patients were monitored for symptoms of delirium using the Confusion Assessment Method. Cognitive and functional statuses were measured with the Mini-Mental State Examination and the Katz and Lawton Index. RESULTS: No statistical differences with regard to symptoms of delirium (p = 0.085), cognitive impairment (p = 0.151), and functional status (p = 0.235) were found between the EG and CG at study entry and at 1 month. After adjustment, statistical differences were found in favor of the EG for symptoms of delirium (p = 0.046), cognitive impairment (p = 0.015), and functional status (p = 0.033). CONCLUSION: Nursing interventions to detect delirium at home are feasible and accepted. The nursing interventions produced a promising effect to improve delirium.