Jörg Aßmus

T regulatory cells and immune activation in Mycobacterium tuberculosis infection and the effect of preventive therapy.

Mycobacterium tuberculosis (TB) often causes persistent infection and many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. We have studied dendritic cell (DC) subsets, regulatory T cells (Treg) and the expression of activation and apoptosis markers on CD4+ and CD8+ T cells in blood from patients with active TB (n = 20), subjects with positive QuantiFERON‐TB GOLD (QFT) test (LTBI, latent TB infection) (n = 20) before and after 3 months of preventive anti‐tuberculous therapy and from QFT‐negative controls (n = 28). The frequency of CD4+CD25+CD127− Treg was highest in the group with active TB (P = 0.001), but also increased in the LTBI group (P = 0.006) compared to controls. The highest level of activated T cells, defined as CD38+HLA‐DR+ cells, was found in the active TB group, for the CD4+ T cell subset positively correlated to the level of CD25+CD127− Treg (P < 0.001, r = 0.4268). After 3 months of preventive therapy, there was an increase in the fraction of foxp3+ Treg, but no differences in markers of activation or apoptosis. In conclusion, there seems to be an increased level of immune activation and Treg in both latent and active TB infection that is only modestly influenced by preventive therapy.

Modulation of Transcriptional and Inflammatory Responses in Murine Macrophages by the Mycobacterium tuberculosis Mammalian Cell Entry (Mce) 1 Complex

The outcome of many infections depends on the initial interactions between agent and host. Aiming at elucidating the effect of the M. tuberculosis Mce1 protein complex on host transcriptional and immunological responses to infection with M. tuberculosis, RNA from murine macrophages at 15, 30, 60 min, 4 and 10 hrs post-infection with M. tuberculosis H37Rv or Δ-mce1 H37Rv was analyzed by whole-genome microarrays and RT-QPCR. Immunological responses were measured using a 23-plex cytokine assay. Compared to uninfected controls, 524 versus 64 genes were up-regulated by 15 min post H37Rv- and Δ-mce1 H37Rv-infection, respectively. By 15 min post-H37Rv infection, a decline of 17 cytokines combined with up-regulation of Ccl24 (26.5-fold), Clec4a2 (23.2-fold) and Pparγ (10.5-fold) indicated an anti-inflammatory response initiated by IL-13. Down-regulation of Il13ra1 combined with up-regulation of Il12b (30.2-fold), suggested switch to a pro-inflammatory response by 4 hrs post H37Rv-infection. Whereas no significant change in cytokine concentration or transcription was observed during the first hour post Δ-mce1 H37Rv-infection, a significant decline of IL-1b, IL-9, IL-13, Eotaxin and GM-CSF combined with increased transcription of Il12b (25.1-fold) and Inb1 (17.9-fold) by 4 hrs, indicated a pro-inflammatory response. The balance between pro-and anti-inflammatory responses during the early stages of infection may have significant bearing on outcome.

Predictors for Return to Work in Subjects with Mild Traumatic Brain Injury

Objective. To predict return to work (RTW) at 12 months for patients who either were sick-listed or were at risk to be sick-listed with persistent postconcussion symptoms (PCS) at six to eight weeks after injury. Method. A prospective cohort study of 151 patients with mild traumatic brain injury (MTBI) admitted consecutively to outpatient clinics at two University Hospitals in Norway. The study was conducted as part of a randomised clinical trial. Injury characteristics were obtained from the medical records. Sick leave data from one year before to one year after MTBI were obtained from the Norwegian Labour and Welfare Service. Self-report questionnaires were used to obtain demographic and symptom profiles. Results. We observed a significant negative association between RTW at 12 months and psychological distress, global functioning, and being sick-listed at two months after MTBI, as well as having been sick-listed the last year before injury. Conclusion. Psychological distress, global functioning postinjury, and the sick leave trajectory of the subjects were negative predictors for RTW. These findings should be taken into consideration when evaluating future vocational rehabilitation models.

Multidisciplinary outpatient treatment in patients with mild traumatic brain injury: A randomised controlled intervention study

ABSTRACT Objective: To evaluate the efficacy of a multidisciplinary outpatient follow-up programme compared to follow-up by a general practitioner for patients being at-risk or sick-listed with persistent post-concussion symptoms two months after a mild traumatic brain injury. Design: Randomised controlled trial. Patients: One hundred fifty-one patients, 16–56 years. Methods: Multidisciplinary outpatient rehabilitation with individual contacts and a psycho-educational group intervention at two outpatient rehabilitation clinics compared to follow-up by a general practitioner after the multidisciplinary examination. Primary outcome was sustainable return-to-work first year post-injury. Secondary outcomes were post-concussion symptoms, disability, the patient’s impressions of change and psychological distress. Results: Days to sustainable return-to-work was 90 in the intervention and 71 in the control group (p = 0.375). The number of post-concussion symptoms were fewer in the intervention (6) compared to the control group (8) at 12 months (p = 0.041). No group differences were observed for disability (p = 0.193), patients impression of change (p = 0.285) or psychological distress (p = 0.716). Conclusion: The multidisciplinary outpatient follow-up programme focusing on better understanding and reassurance of favourable outcome for mild traumatic brain injury did not improve return-to-work, but may have reduced the development of post-concussion symptoms. Additional studies should focus on which factors exhibit a direct impact on return-to-work.

Virtual Reality Training for Upper Extremity in Subacute Stroke (VIRTUES) A multicenter RCT

Objective: To compare the effectiveness of upper extremity virtual reality rehabilitation training (VR) to time-matched conventional training (CT) in the subacute phase after stroke. Methods: In this randomized, controlled, single-blind phase III multicenter trial, 120 participants with upper extremity motor impairment within 12 weeks after stroke were consecutively included at 5 rehabilitation institutions. Participants were randomized to either VR or CT as an adjunct to standard rehabilitation and stratified according to mild to moderate or severe hand paresis, defined as ≥20 degrees wrist and 10 degrees finger extension or less, respectively. The training comprised a minimum of sixteen 60-minute sessions over 4 weeks. The primary outcome measure was the Action Research Arm Test (ARAT); secondary outcome measures were the Box and Blocks Test and Functional Independence Measure. Patients were assessed at baseline, after intervention, and at the 3-month follow-up. Results: Mean time from stroke onset for the VR group was 35 (SD 21) days and for the CT group was 34 (SD 19) days. There were no between-group differences for any of the outcome measures. Improvement of upper extremity motor function assessed with ARAT was similar at the postintervention (p = 0.714) and follow-up (p = 0.777) assessments. Patients in VR improved 12 (SD 11) points from baseline to the postintervention assessment and 17 (SD 13) points from baseline to follow-up, while patients in CT improved 13 (SD 10) and 17 (SD 13) points, respectively. Improvement was also similar for our subgroup analysis with mild to moderate and severe upper extremity paresis. Conclusions: Additional upper extremity VR training was not superior but equally as effective as additional CT in the subacute phase after stroke. VR may constitute a motivating training alternative as a supplement to standard rehabilitation. ClinicalTrials.gov identifier: NCT02079103. Classification of evidence: This study provides Class I evidence that for patients with upper extremity motor impairment after stroke, compared to conventional training, VR training did not lead to significant differences in upper extremity function improvement.

Patient perspectives on continuity of care: adaption and preliminary psychometric assessment of a Norwegian version of the Nijmegen Continuity Questionnaire (NCQ-N)

BackgroundContinuity of care is regarded as a core quality element in healthcare. Continuity can be related to one or more specific caregivers but also applies to collaboration within a team or across boundaries of healthcare. Measuring continuity is important to identify problems and evaluate quality improvement of interventions.This study aimed to assess the feasibility and psychometric properties of a Norwegian version of the Nijmegen Continuity Questionnaire (NCQ).MethodsThe NCQ was developed in The Netherlands. It measures patients’ experienced continuity of care across multiple care settings and as a multidimensional concept regardless of morbidity. The NCQ comprises 28 items categorised into three subscales; two personal continuity scales, “care giver knows me” and “shows commitment”, asked regarding the patient’s general practitioner (GP) and the most important specialist; and one “team/cross boundary continuity” scale, asked regarding primary care, specialised care and cooperation between GP and specialist, with a total of seven factors. The NCQ was translated and adapted to Norwegian (NCQ-N) and distributed among patients referred to somatic rehabilitation (N = 984, response rate 34.5%). Confirmatory factor analyses (CFA), Cronbach’s alpha, intra-class correlation (ICC) and Bland–Altman plots were used to assess psychometric properties.ResultsAll patients (N = 375) who had responded to all parts of the NCQ-N were included in CFA. The CFA fit indices (CFI 0.941, RMSEA 0.064 (95% CI 0.059–0.070), SRMR 0.041) support a seven-factor structure in the NCQ-N based on the three subscales of the original NCQ. Cronbach’s alpha showed internal consistency (0.84–0.97), and was highest for the team/cross-boundary subscales. The NCQ-N showed overall high reliability with ICC 0.84–91 for personal continuity factors and 0.67–0.91 for team factors, with the lowest score for team continuity within primary care.ConclusionsPsychometric assessment of the NCQ-N supports that this instrument, based on the three subscales of the original Dutch NCQ, captures the concept of “continuity of care” among adult patients with a variety of longstanding medical conditions who use healthcare on a regular basis. However, its usefulness among varied patient groups, including younger people, patients with acute disorders and individuals with mental health problems, should be further evaluated.

Communication and Relational Ties in Inter-Professional Teams in Norwegian Specialized Health Care: A Multicentre Study of Relational Coordination

Introduction: The delivery of integrated care depends on the quality of communication and relationships among health-care professionals in inter-professional teams. The main aim of this study was to investigate individual and team communication and relational ties of teams in specific care processes within specialized health care. Methods: This cross-sectional multi-centre study used data from six somatic hospitals and six psychiatric units (N = 263 [response rate, 52%], 23 care processes) using a Norwegian version of the Relational Coordination Survey. We employed linear mixed-effect regression models and one-way analyses of variance. Results: The mean (standard deviation) relational coordination total score ranged from 4.5 (0.33) to 2.7 (0.50). The communication and relationship sub-scale scores were significantly higher within similar functional groups than between contrasting functional groups (P < .05). Written clinical procedures were significantly associated with higher communication scores (P < .05). The proportion of women in a team was associated with higher communication and relationship scores (P < .05). Conclusion: The Relational Coordination Survey shows a marked variation in team functions within inter-professional teams in specialized health-care settings. Further research is needed to determine the reasons for these variations.

Inflammatory Mediator Profiles Differ in Sepsis Patients With and Without Bacteremia

Systemic levels of cytokines are altered during infection and sepsis. This prospective observational study aimed to investigate whether plasma levels of multiple inflammatory mediators differed between sepsis patients with and those without bacteremia during the initial phase of hospitalization. A total of 80 sepsis patients with proven bacterial infection and no immunosuppression were included in the study. Plasma samples were collected within 24 h of hospitalization, and Luminex® analysis was performed on 35 mediators: 16 cytokines, six growth factors, four adhesion molecules, and nine matrix metalloproteases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs). Forty-two patients (52.5%) and 38 (47.5%) patients showed positive and negative blood cultures, respectively. There were significant differences in plasma levels of six soluble mediators between the two “bacteremia” and “non-bacteremia” groups, using Mann–Whitney U test (p < 0.0014): tumor necrosis factor alpha (TNFα), CCL4, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), and TIMP-1. Ten soluble mediators also significantly differed in plasma levels between the two groups, with p-values ranging between 0.05 and 0.0014: interleukin (IL)-1ra, IL-10, CCL2, CCL5, CXCL8, CXCL11, hepatocyte growth factor, MMP-8, TIMP-2, and TIMP-4. VCAM-1 showed the most robust results using univariate and multivariate logistic regression. Using unsupervised hierarchical clustering, we found that TNFα, CCL4, E-selectin, VCAM-1, ICAM-1, and TIMP-1 could be used to discriminate between patients with and those without bacteremia. Patients with bacteremia were mainly clustered in two separate groups (two upper clusters, 41/42, 98%), with higher levels of the mediators. One (2%) patient with bacteremia was clustered in the lower cluster, which compromised most of the patients without bacteremia (23/38, 61%) (χ2 test, p < 0.0001). Our study showed that analysis of the plasma inflammatory mediator profile could represent a potential strategy for early identification of patients with bacteremia.

Psychometric properties of the Norwegian version of the Care Process Self-Evaluation Tool.

ABSTRACT The Care Process Self-Evaluation Tool (CPSET) assesses key characteristics of well-organised care processes in hospitals from an interprofessional team perspective. The present study investigated the psychometric properties of the CPSET in terms of factor structure, convergent and discriminant validity, and reliability in Norwegian language and context. After a pilot test, the Norwegian version of the questionnaire was administered as a web form to 501 health professionals in public general hospitals and mental health specialist services; 301 completed forms (response rate 60%) were returned, and 268 (54%) forms representing 27 care processes (19 from somatic care and 8 from mental healthcare) were included in the valid sample. A confirmatory factor analysis (CFA) confirmed the original five-factor structure. All model fit indices, including the standardised root mean square residual (SRMR), which is independent of the χ2-test, met the criteria for an acceptable model fit. Internal consistencies within sub-scales as measured by Cronbach’s alpha were high (range 0.83–0.94). As expected, some redundancy between factors existed (in particular among the PO (Patient-focused organisation), COR (Coordination of the care process), COM (Communication with patient and family), and PO (Follow-up of the care process) factors). In conclusion, the Norwegian CPSET scale showed acceptable psychometric properties in terms of convergent validity and reliability, and fit indices from the CFA confirmed the original factor structure. Based on these findings, we recommend the Norwegian version of the CPSET for use in the assessment of interprofessional teamwork in care processes in specialist healthcare.

Endocarditis prophylaxis and congenital heart defects in the Norwegian Public Dental Service

The aims of this study are (i) to assess how dental health workers of the Public Dental Service, PDS, carry out endocarditis prophylaxis related to dental treatment for children and adolescents with congenital heart defects (CHD) and to identify factors influencing their appropriate use of guidelines and (ii) to assess how dental health workers perceive any characteristics of patients with CHD.