Arild Faxvaag

TRANSPLANTATION OF ALGINATE MICROCAPSULES: GENERATION OF ANTIBODIES AGAINST ALGINATES AND ENCAPSULATED PORCINE ISLET-LIKE CELL CLUSTERS

BACKGROUND Microencapsulation of islets of Langherhans in alginate poly-L-lysine capsules provides an effective protection against cell-mediated immune destruction, and ideally should allow the transplantation of islets in the absence of immunosuppression. It has previously been suggested that alginate rich in mannuronic acid (high M) is more immunogenic than alginate rich in guluronic acid (high G). The ability of these alginates to induce an antibody response in the recipient or act as an adjuvant to antibody responses against antigens leaked from the capsule was investigated in the present study. METHODS Empty capsules made from these different types of alginate were transplanted intraperitoneally to Wistar rats or Balb/c mice. In addition, some animals were also injected with bovine serum albumin to assess the ability of the alginates to act as an adjuvant to this antigen. Antibody responses to intraperitoneally transplanted free and microencapsulated fetal porcine islet like cell clusters (ICC) were also evaluated, in animals treated with or without cyclosporine. RESULTS Antibodies against high M-alginate capsules were detected in the sera of mice transplanted with this capsule type. However, this response was not seen after the transplantation of high G capsules. When Wistar rats were used as recipients, no antibody responses were detected against any type of alginate capsules. Neither type of capsule acted as an adjuvant. Antibodies against ICC were present, in rats transplanted with both nonencapsulated and encapsulated ICCs. Administration of cyclosporine could abolish this production of antibodies against ICC. CONCLUSIONS High G-alginate capsules are less immunogenic than high M capsules. Because encapsulation did not protect against the generation of antibodies against ICC, it can be assumed that antigen leakage from the capsules occurs, as no evidence was found for capsules breaking in vivo.

Regulation of interleukin-2 and interleukin-6 production from T-cells: Involvement of interleukin-1 β and transforming growth factor-β

Abstract The effect of recombinant (r) interleukin-1β (rIL-1β) and transforming growth factor-β (TGF-β) on the production of interleukin-2 (IL-2) and interleukin-6 (IL-6) from an antigen-specific (LBRM-33-1A5) and an antigen-nonspecific (EL-4-NOB-1) T-cell line was investigated. rIL-1β induced the production of IL-2 and IL-6 from EL-4-NOB-1 cells in a dose-related manner. The LBRM-33-1A5 cells required phytohemagglutinin (PHA) in addition to rIL-1β in order to produce IL-2 and IL-6. IL-2 production was found to precede IL-6 production in both cell lines. No IL-2 or IL-6 production was observed by adding r murine tumor necrosis factor-α or r murine interferon γ to the cells. The presence of 1 ng/ml TGF-β reduced IL-2 and IL-6 production from both T-cell lines by more than 80%. The inhibition of IL-2 and IL-6 production was still evident by a concentration as low as 10 pg/ml of TGF-β. rIL-1β and PHA also stimulated murine thymocytes to produce IL-6 which was inhibited up to 85% in the presence of 1 ng/ml TGF-β. Taken together these results suggest that TGF-β may suppress immune responses by inhibiting the endogenous production of IL-2 and IL-6.

Task-oriented evaluation of electronic medical records systems: development and validation of a questionnaire for physicians

BackgroundEvaluation is a challenging but necessary part of the development cycle of clinical information systems like the electronic medical records (EMR) system. It is believed that such evaluations should include multiple perspectives, be comparative and employ both qualitative and quantitative methods. Self-administered questionnaires are frequently used as a quantitative evaluation method in medical informatics, but very few validated questionnaires address clinical use of EMR systems.MethodsWe have developed a task-oriented questionnaire for evaluating EMR systems from the clinicians perspective. The key feature of the questionnaire is a list of 24 general clinical tasks. It is applicable to physicians of most specialties and covers essential parts of their information-oriented work. The task list appears in two separate sections, about EMR use and task performance using the EMR, respectively. By combining these sections, the evaluator may estimate the potential impact of the EMR system on health care delivery. The results may also be compared across time, site or vendor. This paper describes the development, performance and validation of the questionnaire. Its performance is shown in two demonstration studies (n = 219 and 80). Its content is validated in an interview study (n = 10), and its reliability is investigated in a test-retest study (n = 37) and a scaling study (n = 31).ResultsIn the interviews, the physicians found the general clinical tasks in the questionnaire relevant and comprehensible. The tasks were interpreted concordant to their definitions. However, the physicians found questions about tasks not explicitly or only partially supported by the EMR systems difficult to answer. The two demonstration studies provided unambiguous results and low percentages of missing responses. In addition, criterion validity was demonstrated for a majority of task-oriented questions. Their test-retest reliability was generally high, and the non-standard scale was found symmetric and ordinal.ConclusionThis questionnaire is relevant for clinical work and EMR systems, provides reliable and interpretable results, and may be used as part of any evaluation effort involving the clinicians perspective of an EMR system.

From the Front Line, Report from a Near Paperless Hospital: Mixed Reception Among Health Care Professionals

OBJECTIVE Many Norwegian hospitals that are equipped with an electronic medical record (EMR) system now have proceeded to withdraw the paper-based medical record from clinical workflow. In two previous survey-based studies on the effect of removing the paper-based medical record on the work of physicians, nurses and medical secretaries, we concluded that to scan and eliminate the paper based record was feasible, but that the medical secretaries were the group that reported to benefit the most from the change. To further explore the effects of removing the paper based record, especially in regard to medical personnel, we now have conducted a follow up study of a hospital that has scanned and eliminated its paper-based record. DESIGN A survey of 27 physicians, 60 nurses and 30 medical secretaries was conducted. The results were compared with those from a previous study conducted three years earlier at the same department. MEASUREMENTS The questionnaire (see online Appendix) covered the frequency of use of the EMR system for specific tasks by physicians, nurses and medical secretaries, the ease of performing these tasks compared to previous routines, user satisfaction and computer literacy. RESULTS Both physicians and nurses displayed increased use of the EMR compared to the previous study, while medical secretaries reported generally unchanged but high use. CONCLUSION The increase in use was not accompanied by a similar change in factors such as computer literacy or technical changes, suggesting that these typical success factors are necessary but not sufficient.

What Influences Patient Participation in an Online Forum for Weight Loss Surgery? A Qualitative Case Study

Background Many patients who undergo weight loss (bariatric) surgery seek information and social support in online discussion forums, but the vast amount of available information raises concerns about the impact of such information. A secure online discussion forum was developed and offered to bariatric surgery patients. The forum was moderated and allowed contact with peers and health care professionals. Objective The purposes of this study were to explore how individuals undergoing bariatric surgery used the moderated discussion forum and to better understand what influenced their participation in the forum. Methods The study was designed as an explorative case study. We conducted participant observation of the discussion forum over a time period of approximately six months. For further insight, we carried out in-depth semistructured interviews with seven patients who had access to the forum. We analyzed the material inductively, using content and thematic analysis. Results The patients used the forum as an arena in which to interact with peers and providers, as well as to provide and achieve informational and social support. The analysis suggests that there are three major themes that influenced participation in the online discussion forum: (1) the participant’s motivation to seek information, advice, and guidance, (2) the need for social support and networking among peers, and (3) concerns regarding self-disclosure. Conclusions The findings of this study imply that a moderated discussion forum for bariatric surgery patients has potential for use in a therapeutic context. The discussion forum fulfilled the informational and support needs of the bariatric surgery patients and was particularly useful for those who excluded themselves from the traditional program and experienced barriers to expressing their own needs. Even though our findings imply that the patients benefitted from using the forum regardless of their active or passive participation, restraining factors, such as considerations regarding self-disclosure, must be further investigated to prevent certain users from being precluded from participation.

Multiple phospholipase A2 enzymes participate in the inflammatory process in osteoarthritic cartilage.

Objective: The aim of this study was to determine the involvement of pro-inflammatory phospholipase A2 (PLA2) enzymes in human chondrocytes from patients with osteoarthritis (OA). Methods: PLA2 involvement in OA chondrocytes was analysed by (a) arachidonic acid (AA) and oleic acid release, (b) PLA2 mRNA analysis, and (c) prostaglandin E2 (PGE2) production in cultured OA chondrocytes in response to various cytokines and platelet activating factor (PAF). Results: Pro-inflammatory cytokines and PAF stimulation led to increased AA release, interleukin (IL)-1β and tumour necrosis factor (TNF) being the strongest inducers. The pattern of oleic acid release was similar to but less prominent than AA release, suggesting that predominantly arachidonyl selective enzymes were activated. IL-1β, TNF, IL-6, and IL-8 upregulated secretory group IIA, IID, and V phospholipase A2 (sPLA2-IIA, -IID, -V) and cytosolic group IVA phospholipase A2 (cPLA2-IVA) expression, where induction of chondrocyte sPLA2-IID is a novel finding. Furthermore, IL-1β, TNF, and IL-6 also induced COX2 expression. PAF induced expression of group IIA, IID and IVA PLA2, and COX2. In line with its anti-inflammatory properties, IL-4 was unable to induce either AA release or expression of PLA2s or COX2. IL-1β and TNF strongly increased PGE2 production, with IL-1β as the most prominent inducer. Conclusion: Multiple PLA2 isoforms are expressed and influenced by pro-inflammatory stimuli in OA chondrocytes. Hence, several PLA2 enzymes may contribute to chondrocyte function by their upregulation and activation, and increased AA release and PGE2 production may therefore be important effectors in OA pathophysiology. PLA2 enzymes and cPLA2-IVA in particular are thus possible therapeutic targets in OA.

The Impact of an eHealth Portal on Health Care Professionals’Interaction with Patients: Qualitative Study

Background People who undergo weight loss surgery require a comprehensive treatment program to achieve successful outcomes. eHealth solutions, such as secure online portals, create new opportunities for improved health care delivery and care, but depend on the organizational delivery systems and on the health care professionals providing it. So far, these have received limited attention and the overall adoption of eHealth solutions remains low. In this study, a secure eHealth portal was implemented in a bariatric surgery clinic and offered to their patients. During the study period of 6 months, 60 patients and 5 health care professionals had access. The portal included patient information, self-management tools, and communication features for online dialog with peers and health care providers at the bariatric surgery clinic. Objective The aim of this study was to characterize and assess the impact of an eHealth portal on health care professionals’ interaction with patients in bariatric surgery. Methods This qualitative case study involved a field study consisting of contextual interviews at the clinic involving observing and speaking with personnel in their actual work environment. Semi-structured in-depth interviews were conducted with health care professionals who interacted with patients through the portal. Analysis of the collected material was done inductively using thematic analysis. Results The analysis revealed two main dimensions of using an eHealth portal in bariatric surgery: the transparency it represents and the responsibility that follows by providing it. The professionals reported the eHealth portal as (1) a source of information, (2) a gateway to approach and facilitate the patients, (3) a medium for irrevocable postings, (4) a channel that exposes responsibility and competence, and (5) a tool in the clinic. Conclusions By providing an eHealth portal to patients in a bariatric surgery program, health care professionals can observe patients’ writings and revelations thereby capturing patient challenges and acting and implementing measures. Interacting with patients through the portal can prevent dropouts and deterioration of patients’ health. However, professionals report on organizational challenges and personal constraints related to communicating with patients in writing online. Further development of guidelines and education of health care professionals about how to handle, prioritize, communicate, and facilitate patients online is required in addition to increased attention to the organizational infrastructures and incentives for enabling such solutions in health care.

A low oncogenic variant of friend murine leukemia virus with strong immunosuppressive properties

SummaryFriend leukemia complex (FLC) is known to induce immunosuppression but the use of FLC in studies of immune cells function is disadvantageous since the immunosuppression always is accompanied by an acute erythroleukemia. To obtain immunosuppressive variants of FLC with reduced leukemogenic potential, we isolated T-helper cells from FLC infected mice, and passed lysates of the cells to recipient uninfected mice. A group of these mice developed a condition distinct from the disease induced by FLC. A viral stock prepared from these mice, designated Fd-MIV for friend derived murine immunodefiency virus, induced a profound suppression of the primary antibody response without acute transformation in adult NMRI mice. Terminally a wasting disease with weight loss, atrophy of the thymus and lymph nodes and renal disease was observed in some mice. Analysis of viral DNA and RNA from infected NIH 3T3 cells showed that Fd-MIV contained at least two viral components, a 8.4 kb friend murine leukemia virus (F-MuLV) and a 7.4kb mink cell focus (MCF) / xenotropic virus related genome. The 7.4 kb genome was not detected in Fd-MIV infected, immunocompromised mice indicating that the 8.4kb genome might be responsible for the disease.

Nordic eHealth Indicators: Organisation of research, first results and plan for the future.

eHealth indicator and benchmarking activities are rapidly increasing nationally and internationally. The work is rarely based on a transparent methodology for indicator definition. This article describes first results of testing an indicator methodology for defining eHealth indicators, which was reported at the Medical Informatics Europe conference in 2012. The core elements of the methodology are illustrated, demonstrating validation of each of them in the context of Nordic eHealth Indicator work. Validation proved the importance of conducting each of the steps of the methodology, with several scientific as well as practical outcomes. The article is based on a report to be published by the Nordic Council of Ministers [4].

Beyond the EPR: Complementary roles of the hospital-wide electronic health record and clinical departmental systems

BackgroundMany hospital departments have implemented small clinical departmental systems (CDSs) to collect and use patient data for documentation as well as for other department-specific purposes. As hospitals are implementing institution-wide electronic patient records (EPRs), the EPR is thought to be integrated with, and gradually substitute the smaller systems. Many EPR systems however fail to support important clinical workflows. Also, successful integration of systems has proven hard to achieve. As a result, CDSs are still in widespread use. This study was conducted to see which tasks are supported by CDSs and to compare this to the support offered by the EPR.MethodsSemi-structured interviews with users of 16 clinicians using 15 different clinical departmental systems (CDS) at a Medium-sized University hospital in Norway. Inductive analysis of transcriptions from the audio taped interviews.ResultsThe roles of CDSs were complementary to those of the hospital-wide EPR system. The use of structured patient data was a characteristic feature. This facilitated quality development and supervision, tasks that were poorly supported by the EPR system. The structuring of the data also improved filtering of information to better support clinical decision-making. Because of the high value of the structured patient data, the users put much effort in maintaining their integrity and representativeness. Employees from the departments were also engaged in the funding, development, implementation and maintenance of the systems.ConclusionClinical departmental systems are vital to the activities of a clinical hospital department. The development, implementation and clinical use of such systems can be seen as bottom-up, user-driven innovations.