27 research outputs found

    Biomarkers in sepsis and other severe infections

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    Infectious diseases constitute a major global health problem. The presenting clinical picture results from a mixture of direct toxic actions by the microbiological agent and of the immune response mounted by the host. There is often a rapid onset, which may constitute a diagnostic and therapeutic challenge, whereas in other cases an extensive investigation over a long time period can fail to identify a causal microbial agent. The aim with this thesis was to study the cellular immune response with phenotypical assays, in patients with severe infections with focus on sepsis. We assessed if our findings could serve as biomarkers and provide valuable diagnostic and possible also therapeutic information. In the first part (paper I) we examined surface markers on white blood cells from patients with severe infections. In some instances our analysis could differentiate between infections of bacterial and viral origin. In the second part (paper II-IV) we examined the incidence and nature of the immune alterations found in patients with sepsis and septic shock. We identified a protein (Wnt5a) that inhibited differentiation of monocytes to monocyte-derived myeloid dendritic cells (Mo-mDC), which may play a role in the DC depletion often seen in sepsis. Also, as indicated by cell surface phenotype, a large inter-individual variation of immune activation and immunosuppression was detected in patients with sepsis, with a dominance of immunosuppression in patients with septic shock. Finally, different types of immature myeloid immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) were found in patients with sepsis; Mo-MDSCs were preferentially expanded in patients with gram-negative sepsis, whereas granulocytic MDSCs (PMN-MDSCs) accumulated in patients with gram-positive sepsis. We conclude that the immune response during severe infections shows large inter-individual variations and biomarker guided therapy could be useful in individualised treatment

    ‘Managing pieces of a personal puzzle’ — older people’s experiences of self-management falls prevention exercise guided by a digital program or a booklet

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    Background: Exercise is effective in order to prevent falls in community-dwelling older people. Self-management programs have the potential to increase access and reduce costs related to exercise-based fall prevention. However, information regarding older people's views of participating in such programs is needed to support implementation. The aim of this study was to explore older people's experiences of a self-management fall prevention exercise routine guided either by a digital program (web-based or mobile) or a paper booklet. Methods: This qualitative study was part of a feasibility study exploring two completely self-managed exercise interventions in which the participants tailored their own program, guided either by a digital program or a paper booklet. Individual face-to-face semi-structured interviews were conducted with a purposeful sample of 28 participants (18 women), mean age 76yrs. Qualitative content analysis was used to analyse the data. Results: Self-managing and self-tailoring these exercise programs was experienced as Managing pieces of a personal puzzle'. To independently being able to create a program and manage exercise was described in the categories Finding my own level' and Programming it into my life'. The participants experienced the flexibility and independence provided by completely self-managed exercise as positive and constructive although it required discipline. Furthermore, different needs and preferences when managing their exercise were described, as well as varying sources of motivation for doing the exercise, as highlighted in the category Defining my source of motivation'. The category Evolving my acquired knowledge' captures the participants' views of building their competence and strategies for maintenance of the exercise. It describes a combined process of learning the program and developing reflection, which was more clearly articulated by participants using the digital program. Conclusions: This study provides new knowledge regarding experiences, preferences and motivations of older people to engage in home-based self-managed fall prevention exercise. They expressed both a capability and willingness to independently manage their exercise. A digital program seems to have strengthened the feeling of support while creating their own exercise program and tailoring it to their preferences and circumstances, which might therefore create better opportunities for adoption and adherence in the long term

    Lymphocyte and monocyte flow cytometry immunophenotyping as a diagnostic tool in uncharacteristic inflammatory disorders

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    <p>Abstract</p> <p>Background</p> <p>Patients with uncharacteristic inflammatory symptoms such as long-standing fatigue or pain, or a prolonged fever, constitute a diagnostic and therapeutic challenge. The aim of the present study was to determine if an extended immunophenotyping of lymphocytes and monocytes including activation markers can define disease-specific patterns, and thus provide valuable diagnostic information for these patients.</p> <p>Methods</p> <p>Whole blood from patients with gram-negative bacteraemia, neuroborreliosis, tuberculosis, acute mononucleosis, influenza or a mixed connective tissue disorders, as diagnosed by routine culture and serology techniques was analysed for lymphocyte and monocyte cell surface markers using a no-wash, no-lyse protocol for multi-colour flow cytometry method. The immunophenotyping included the activation markers HLA-DR and CD40. Plasma levels of soluble TNF alpha receptors were analysed by ELISA.</p> <p>Results</p> <p>An informative pattern was obtained by combining two of the analysed parameters: (i), the fractions of HLA-DR-expressing CD4+ T cells and CD8+ T cells, respectively, and (ii), the level of CD40 on CD14+ CD16- monocytes. Patients infected with gram-negative bacteria or EBV showed a marked increase in monocyte CD40, while this effect was less pronounced for tuberculosis, borrelia and influenza. The bacterial agents could be distinguished from the viral agents by the T cell result; CD4+ T cells reacting in bacterial infection, and the CD8+ T cells dominating for the viruses. Patients with mixed connective tissue disorders also showed increased activation, but with similar engagement of CD4+ and CD8+ T cells. Analysis of soluble TNF alpha receptors was less informative due to a large inter-individual variation.</p> <p>Conclusion</p> <p>Immunophenotyping including the combination of the fractions of HLA-DR expressing T cell subpopulations with the level of CD40 on monocytes produces an informative pattern, differentiating between infections of bacterial and viral origin. Furthermore, a quantitative analysis of these parameters revealed the novel finding of characteristic patterns indicating a subacute bacterial infection, such as borreliosis or tuberculosis, or a mixed connective tissue disorder. The employed flow cytometric method is suitable for clinical diagnostic laboratories, and may help in the assessment of patients with uncharacteristic inflammatory symptoms.</p

    Older adults as designers of behavior change strategies to increase physical activity : report of a participatory design process

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    Background: Despite the significant value of physical activity for the health of older adults, this population often fails to achieve recommended activity levels. Digital interventions show promise in providing support for self-managed physical activity. However, more information is needed about older adults' preferences for digital support to change physical activity behaviors as well as the process of designing them. The aim of this paper was to describe the participatory design process in which older adults were involved in the co-creation of digitally supported behavioral change strategies to support self-managed physical activity, and how the results were integrated in a prototype. Methods: The participatory design process involved with nine older adults and two researchers. The participants were divided in two groups, and each group participated in three workshops and completed home tasks in between workshops. Following an iterative design process influenced by theories of behavior change, the workshops and home tasks were continuously analyzed, and the content and process were developed between groups and the next set of workshops. Prototypes of a mobile health (mHealth) solution for fall preventive exercise for older adults were developed in which the conceptualized strategies were integrated. To support coherence in reporting and evaluation, the developed techniques were mapped to the Behavior Change Technique Taxonomy v1 and the basic human psychosocial needs according to the Self-determination Theory. Results: The results highlight different preferences of older adults for feedback on physical activity performance, as well as the importance of transparency regarding the identification of the sender of feedback. Preferences for content and wording of feedback varied greatly. Subsequently, the design process resulted in a virtual health coach with three different motivational profiles and tools for goal setting and self-monitoring. These behavior change strategies were integrated in the exercise application Safe Step v1. The conformity of the design concepts with the needs of Self-determination Theory and Behavior Change Technique Taxonomy v1 are presented. Conclusion: The participatory design process exemplifies how older adults successfully contributed to the design of theory-based digital behavior change support, from idea to finished solution. Tailoring feedback with a transparent sender is important to support and not undermine motivation

    Patterns and predictors of sick leave among Swedish non-hospitalized healthcare and residential care workers with Covid-19 during the early phase of the pandemic

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    Healthcare and residential care workers represent two occupational groups that have, in particular, been at risk of Covid-19, its long-term consequences, and related sick leave. In this study, we investigated the predictors of prolonged sick leave among healthcare and residential workers due to non-hospitalized Covid-19 in the early period of the pandemic. This study is based on a patient register (n = 3209) and included non-hospitalized healthcare or residential care service workers with a positive RT- PCR for SARS-CoV-2 (n = 433) between March and August 2020. Data such as socio-demographics, clinical characteristics, and the length of sick leave because of Covid-19 and prior to the pandemic were extracted from the patient’s electronic health records. Prolonged sick leave was defined as sick leave ≥ 3 weeks, based on the Swedish pandemic policy. A generalized linear model was used with a binary distribution, adjusted for age, gender, and comorbidity in order to predict prolonged sick leave. Of 433 (77% women) healthcare and residential care workers included in this study, 14.8% needed longer sick leave (&gt; 3 weeks) due to Covid-19. Only 1.4% of the subjects were on sick leave because of long Covid. The risk of sick leave was increased two-fold among residential care workers (adjusted RR 2.14 [95% CI 1.31–3.51]). Depression/anxiety (adjusted RR 2.09 [95% CI 1.31–3.34]), obesity (adjusted RR 1.96 [95% CI 1.01–3.81]) and dyspnea at symptom onset (adjusted RR 2.47 [95% CI 1.55–3.92]), sick leave prior to the pandemic (3–12 weeks) (adjusted RR 2.23 [95% CI 1.21–4.10]) were associated with longer sick leave. From a public health perspective, considering occupational category, comorbidity, symptoms at onset, and sick leave prior to the pandemic as potential predictors of sick leave in healthcare may help prevent staff shortage

    Agreement between reported questionnaire data and medical records on diagnosis and COVID-19 symptoms at onset

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    The aim of this study was to assess whether there was agreement between self-reported data in a survey and medical records regarding diagnoses and symptoms at COVID-19 onset. The impact of sociodemographic factors on agreement between the two data sources was also assessed. Cross-sectional data were extracted from a Swedish longitudinal cohort study. In total, 401 non-hospitalized patients with a polymerase chain reaction-confirmed COVID-19 infection responded to a survey and agreed to a review of their electronic medical records. Agreement, estimated using the kappa statistic, sensitivity, and specificity were calculated for nine diagnoses and eleven symptoms. Differences between subgroups based on sociodemographic factors were assessed. The agreement between the self-reported data and medical records was at a substantial to moderate level for diagnoses such as diabetes mellitus (kappa 0.65, sensitivity 86%) and hypertension (kappa 0.59, sensitivity 56%) and at a fair level for more difficult-to-define conditions such as ongoing immunosuppressive treatment (kappa 0.27, sensitivity 25%). The agreement between the two data sources on symptoms was between fair and poor (kappa 0.36 for fever; kappa 0.05 for fatigue). Agreement for some diagnoses and symptoms varied across some sociodemographic subgroups, e.g. agreement in diabetes mellitus was significantly better in males (kappa 1.0) than females (kappa 0.52, homogeneity tests p = 0.02). In general, kappa values were lower for symptoms than diagnoses. The agreement between the two sources varied with diagnoses and symptoms and was also influenced by sociodemographic factors. This study illustrates that it is important to consider type of data used in the epidemiological studies as different information sources differ with quality and accuracy

    Predictors of post-COVID-19 and the impact of persistent symptoms in non-hospitalized patients 12 months after COVID-19, with a focus on work ability

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    Background: Better knowledge of long-term symptoms following coronavirus disease 2019 (COVID-19), the so-called post-COVID-19, in non-hospitalized patients is needed. The aim of this study was to study persisent symptoms up to 12 months after COVID-19 in non-hospitalized patients and their impact on work ability. We also investigated predictors of persistent symptoms. Methods: This study encompassed non-hospitalized adult subjects with a COVID-19 infection confirmed via positive nasopharyngeal swab polymerase chain reaction test during the first wave of the pandemic in Uppsala, Sweden. In total, 566 subjects were sent a survey via e-mail or post with an invitation to participate in the survey 12 months post-diagnosis. The majority of subjects were healthcare workers, as this group was prioritized for testing. Results: A total of 366 subjects responded, with 47% reporting persistent symptoms 12 months after their COVID-19 diagnosis. The most commonly reported symptoms at this time were impaired sense of smell and/or taste and fatigue. Among the predictors of persistent symptoms were being born abroad, lower physical fitness compared with peers before COVID-19, body mass index &gt;25 kg/m2, cooccurrence of hypertension and chronic pain, and having more than seven of the general COVID-19 symptoms at the onset. Respondents with symptoms after 12 months self-reported negatively about their general health and work ability. Conclusions: This study indicated that many people who had mild COVID-19 might have a variety of long-term symptoms. It highlights the importance of considering work ability after mild COVID-19
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