| 1. |
- Gyllemark, Paula, et al.
(författare)
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Are other tick-borne infections overlooked in patients investigated for Lyme neuroborreliosis? : A large retrospective study from South-eastern Sweden
- 2021
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Ingår i: Ticks and Tick-borne Diseases. - : Elsevier GMBH. - 1877-959X .- 1877-9603. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- In Europe, the hard tick Ixodes ricinus is considered the most important vector of human zoonotic diseases. Human pathogenic agents spread by I. ricinus in Sweden include Borrelia burgdorferi sensu lato (s.l.), Anaplasma phagocytophilum, Rickettsia helvetica, the recently described Neoehrlichia mikurensis, Borrelia miyamotoi, tick-borne encephalitis virus (TBEV), and Babesia spp. (Babesia microti, Babesia venatorum and Babesia divergens). Since these pathogens share the same vector, co-infections with more than one tick-borne pathogen may occur and thus complicate the diagnosis and clinical management of the patient due to possibly altered symptomatology. Borrelia burgdorferi s.l., TBEV and B. miyamotoi are well-known to cause infections of the central nervous system (CNS), whereas the abilities of other tick-borne pathogens to invade the CNS are largely unknown. The aim of this study was to investigate the presence and clinical impact of tick-borne pathogens other than B. burgdorferi s.l. in the cerebrospinal fluid (CSF) and serum samples of patients who were under investigation for Lyme neuroborreliosis (LNB) in a tick-endemic region of South-eastern Sweden. CSF and serum samples from 600 patients, recruited from the Regions of center dot Ostergo center dot tland County, Jo center dot nko center dot ping County and Kalmar County in South-eastern Sweden and investigated for LNB during the period of 2009-2013, were retrospectively collected for analysis. The samples were analysed by real-time PCR for the presence of nucleic acid from B. burgdorferi s.l., B. miyamotoi, A. phagocytophilum, Rickettsia spp., N. mikurensis, TBEV and Babesia spp. Serological analyses were conducted in CSF and serum samples for all patients regarding B. burgdorferi s.l., and for the patients with CSF mononuclear pleocytosis, analyses of antibodies to B. miyamotoi, A. phagocytophilum, spotted fever group (SFG) rickettsiae, TBEV and B. microti in serum were performed. The medical charts of all the patients with CSF mononuclear pleocytosis and patients with positive PCR findings were reviewed. Of the 600 patients, 55 (9%) presented with CSF mononuclear pleocytosis, 13 (2%) of whom had Borrelia-specific antibodies in the CSF. One patient was PCRpositive for N. mikurensis, and another one was PCR-positive for Borrelia spp. in serum. No pathogens were detected by PCR in the CSF samples. Four patients had serum antibodies to B. miyamotoi, four patients to A. phagocytophilum, five patients to SFG rickettsiae, and six patients to TBEV. One patient, with antibodies to SFG
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| 2. |
- Håkansson, Anders, et al.
(författare)
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Effects and Limitations of a Unique, Nationwide, Self-Exclusion Service for Gambling Disorder and Its Self-Perceived Effects and Harms in Gamblers : Protocol for a Qualitative Interview Study
- 2023
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Ingår i: JMIR Research Protocols. - 1929-0748. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Voluntary self-exclusion from gambling is a common but underdeveloped harm reduction tool in the management of gambling problems or gambling disorders. Large-scale, multi-operator, and operator-independent self-exclusion services are needed. A recent nationwide multi-operator self-exclusion service in Sweden (Spelpaus), involving both land- and web-based gambling sites, is promising, but recent data have revealed limitations to this system and possibilities to breach one’s self-exclusion through overseas web-based gambling. More knowledge is needed about the benefits and challenges of such an extensive self-exclusion service, and its effects as perceived by gamblers. Objective: This study protocol describes the rationale and design of a qualitative interview study addressing the effects and limitations perceived by individuals with gambling problems and their concerned significant others. The study aims to provide an in-depth experience of this novel self-exclusion service and to inform stakeholders and policymakers in order to further improve harm reduction tools against gambling problems. Methods: Individuals with gambling problems will be recruited primarily through social media and also from a treatment unit, if needed, for a qualitative interview study. Recorded interview material will be analyzed through content analysis, and recruitment will continue until saturation in the material is reached. This study will provide in-depth information about a harm reduction tool that is promising and commonly used, but which has proven to be breached by a significant number of users, potentially limiting its efficiency. The aim is to interview a sufficient number of gamblers until saturation has been obtained in the interview material. Saturation will be considered through a continuous analysis, comparing recently collected data to previously collected data. Results: Results will be reported as the themes and subthemes identified after the thorough analysis and coding of the transcribed text material and will be accompanied by citations representing relevant themes and subthemes. Results are planned to be provided before the end of 2023. Conclusions: This study will likely provide new insights into user perspectives on a multi-operator self-exclusion service that involves both web- and land-based gambling operators, and which according to previous literature attracts many gamblers but also appears to have limitations and challenges in the target group of individuals with gambling problems. Policy and legislation implications, as well as clinical implications for treatment providers, will be discussed. Results and conclusions will be disseminated to policy makers in Sweden and internationally, as well as to peer organizations, treatment providers, and the research community.
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| 3. |
- Jonsson Henningsson, Anna, et al.
(författare)
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Laboratory Methods for Detection of Infectious Agents and Serological Response in Humans With Tick-Borne Infections : A Systematic Review of Evaluations Based on Clinical Patient Samples
- 2021
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Ingår i: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Background: For the most important and well-known infections spread by Ixodes ticks, Lyme borreliosis (LB) and tick-borne encephalitis (TBE), there are recommendations for diagnosis and management available from several health authorities and professional medical networks. However, other tick-borne microorganisms with potential to cause human disease are less known and clear recommendations on diagnosis and management are scarce. Therefore, we performed a systematic review of published studies and reviews focusing on evaluation of laboratory methods for clinical diagnosis of human tick-borne diseases (TBDs), other than acute LB and TBE. The specific aim was to evaluate the scientific support for laboratory diagnosis of human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis, babesiosis, hard tick relapsing fever, tularemia and bartonellosis, as well as tick-borne co-infections and persistent LB in spite of recommended standard antibiotic treatment.Methods: We performed a systematic literature search in 11 databases for research published from 2007 through 2017, and categorized potentially relevant references according to the predefined infections and study design. An expert group assessed the relevance and eligibility and reviewed the articles according to the QUADAS (diagnostic studies) or AMSTAR (systematic reviews) protocols, respectively. Clinical evaluations of one or several diagnostic tests and systematic reviews were included. Case reports, non-human studies and articles published in other languages than English were excluded.Results: A total of 48 studies fulfilled the inclusion criteria for evaluation. The majority of these studies were based on small sample sizes. There were no eligible studies for evaluation of tick-borne co-infections or for persistent LB after antibiotic treatment.Conclusions: Our findings highlight the need for larger evaluations of laboratory tests using clinical samples from well-defined cases taken at different time-points during the course of the diseases. Since the diseases occur at a relatively low frequency, single-center cross-sectional studies are practically not feasible, but multi-center case control studies could be a way forward.
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| 4. |
- Lindahl, Jesper, et al.
(författare)
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Add-on pramipexole for anhedonic depression : study protocol for a randomised controlled trial and open-label follow-up in Lund, Sweden
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 13:11, s. 9
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Many depressed patients do not achieve remission with available treatments. Anhedonia is a common residual symptom associated with treatment resistance as well as low function and quality of life. There are currently no specific and effective treatments for anhedonia. Some trials have shown that dopamine agonist pramipexole is efficacious for treating depression, but more data is needed before it could become ready for clinical prime time. Given its mechanism of action, pramipexole might be a useful treatment for a depression subtype characterised by significant anhedonia and lack of motivation-symptoms associated with dopaminergic hypofunction. We recently showed, in an open-label pilot study, that add-on pramipexole is a feasible treatment for depression with significant anhedonia, and that pramipexole increases reward-related activity in the ventral striatum. We will now confirm or refute these preliminary results in a randomised controlled trial (RCT) and an open-label follow-up study. METHODS AND ANALYSIS: Eighty patients with major depression (bipolar or unipolar) or dysthymia and significant anhedonia according to the Snaith Hamilton Pleasure Scale (SHAPS) are randomised to either add-on pramipexole or placebo for 9 weeks. Change in anhedonia symptoms per the SHAPS is the primary outcome, and secondary outcomes include change in core depressive symptoms, apathy, sleep problems, life quality, anxiety and side effects. Accelerometers are used to assess treatment-associated changes in physical activity and sleep patterns. Blood and brain biomarkers are investigated as treatment predictors and to establish target engagement. After the RCT phase, patients continue with open-label treatment in a 6-month follow-up study aiming to assess long-term efficacy and tolerability of pramipexole. ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. The study is externally monitored according to Good Clinical Practice guidelines. Results will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05355337 and NCT05825235.
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| 5. |
- Suneson, Klara, et al.
(författare)
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Efficacy of eicosapentaenoic acid in inflammatory depression : study protocol for a match-mismatch trial
- 2022
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Ingår i: BMC Psychiatry. - : Springer Science and Business Media LLC. - 1471-244X. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most antidepressant treatment studies have included patients strictly based on the Diagnostic and Statistical Manual of Mental Disorders definition of Major Depressive Disorder (MDD). Given the heterogeneity of MDD, this approach may have obscured inter-patient differences and hampered the development of novel and targeted treatment strategies. An alternative strategy is to use biomarkers to delineate endophenotypes of depression and test if these can be targeted via mechanism-based interventions. Several lines of evidence suggest that “inflammatory depression” is a clinically meaningful subtype of depression. Preliminary data indicate that omega-3 fatty acids, with their anti-inflammatory and neuroprotective properties, may be efficacious in this subtype of depression, and this study aims to test this hypothesis. Method: We conduct a match-mismatch-trial to test if add-on omega-3 fatty acid eicosapentaenoic acid (EPA) reduces depressive symptoms in patients with MDD and systemic low-grade inflammation. MDD patients on a stable antidepressant treatment are stratified at baseline on high sensitivity-C-reactive protein (hs-CRP) levels to a high-inflammation group (hs-CRP ≥ 3 mg/L) or a low-inflammation group (hs-CRP < 3 mg/L). Both groups receive add-on EPA (2 g per day) for 8 weeks with three study visits, all including blood draws. Patients and raters are blind to inflammation status. Primary outcome measure is change in Hamilton Depression Rating Scale score between baseline and week 8. We hypothesize that the inflammation group has a superior antidepressant response to EPA compared to the non-inflammation group. Secondary outcomes include a composite score of “inflammatory depressive symptoms”, quality of life, anxiety, anhedonia, sleep disturbances, fatigue, cognitive performance and change in biomarkers relating to inflammation, oxidative stress, metabolomics and cellular aging. Discussion: In this study we will, for the first time using a match-mismatch trial design, test if omega-3 is an efficacious treatment for inflammatory depression. If our study is successful, it could add to the field of precision psychiatry. Trial registration: This trial was registered May 8, 2017 on clinicaltrials.gov under the reference number NCT03143075.
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| 6. |
- Suneson, Klara, et al.
(författare)
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Omega-3 fatty acids for inflamed depression - A match/mismatch study
- 2024
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Ingår i: Brain, Behavior, and Immunity. - 1090-2139. ; 118, s. 192-201
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of research on the pathophysiology of depression, the development of new therapeutic interventions has been slow, and no biomarkers of treatment response have been clinically implemented. Several lines of evidence suggest that the clinical and biological heterogeneity among patients with major depressive disorder (MDD) has hampered progress in this field. MDD with low-grade inflammation - "inflamed depression" - is a subtype of depression that may be associated with a superior antidepressant treatment response to anti-inflammatory compounds. Omega-3 fatty acid eicosapentaenoic acid (EPA) has anti-inflammatory properties, and preliminary data suggest that it may be particularly efficacious in inflamed depression. In this study we tested the hypothesis that add-on EPA has greater antidepressant efficacy in MDD patients with high baseline high-sensitivity C-reactive protein (hs-CRP) compared to MDD patients with low hs-CRP. All subjects received 2.2 g EPA, 400 mg docosahexaenoic acid and 800 mg of other fatty acids daily for 8 weeks, added to stable ongoing antidepressant treatment. The primary outcome was change in the 17-item Hamilton Depression Rating Scale (HAMD-17). Patients and raters were blind to baseline hs-CRP status. In an intention-to-treat analysis including all subjects with at least one post baseline visit (n = 101), ahs-CRPcut-off of ≥1 mg/L, but not ≥3 mg/L, was associated with a greater improvement in HAMD-17 total score. In addition to a general antidepressant effect among patients with hs-CRP ≥ 1 mg/L, adjuvant EPA treatment improved symptoms putatively related to inflamed depression such as fatigue and sleep difficulties. This adds to the mounting evidence that delineation of MDD subgroups based on inflammation may be clinically relevant to predict treatment response to anti-inflammatory interventions.
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| 7. |
- Tjernberg, Ivar, et al.
(författare)
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Cerebrospinal fluid markers of inflammation and brain injury in Lyme neuroborreliosis - a prospective follow-up study
- 2022
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : WALTER DE GRUYTER GMBH. - 1434-6621 .- 1437-4331. ; 60:7, s. 1124-1132
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study was to evaluate levels and kinetics of cerebrospinal fluid (CSF) markers of inflammation and brain injury in patients with Lyme neuroborreliosis (LNB). Methods Adult patients with clinically suspected LNB were enrolled, in a prospective clinical study in the South East of Sweden. Patients were classified according to the European Federation of Neurological Societies guidelines. Definite cases of LNB were re-examined one month later including a repeat CSF investigation. Routine laboratory parameters were investigated along with CSF levels of neurodegenerative markers glial fibrillary acidic protein (GFAp), total tau (t-tau) and neurofilament light protein (NFL), as well as neuroinflammatory markers soluble triggering receptor expressed on myeloid cells 2 (sTREM2), YKL-40 and CXCL13. Non-LNB served as controls. An additional comparison group consisted of spinal anesthesia subjects (SAS) without known central nervous system conditions. Results CSF levels of sTREM2 and CXCL13 were elevated in definite LNB patients at diagnosis compared with non-LNB patients (p<0.001) and SAS (p <= 0.01). In addition, CSF levels of sTREM2, YKL-40 and CXCL13 rapidly declined in at follow-up after antibiotic treatment. In contrast, CSF levels of GFAp and t-tau did not differ across LNB groups, and did not change after treatment. Conclusions Although in a limited number of LNB patients, the results indicate a predominance of microglial and neuroinflammatory involvement rather than parenchymal CNS injury in CSF at diagnosis of LNB with a prompt decline after antibiotic treatment. The findings provide pathogenetic insights and may be of value in differential diagnosis of CSF findings.
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| 8. |
- Tjernberg, Johanna, et al.
(författare)
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Older persons’ thoughts about death and dying and their experiences of care in end-of-life: a qualitative study
- 2020
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Ingår i: Nursing Open. - : Springer Science and Business Media LLC. - 2054-1058. ; 19, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFew studies have focused on how older persons living in nursing homes perceive their last period of life. Furthermore, previous research on older persons’ perceptions of death and dying is limited. Hence, there is an urgent need to explore their experiences during their final period in life.AimTo explore thoughts about death and dying and experiences of care in end-of-life among older persons living in nursing homes.MethodsThis study employed a qualitative approach including individual interviews with 36 older persons living in Swedish nursing homes. Questions related to quality of life; physical health; thoughts about death, dying, and the future; and experiences related to the living condition and environment were asked. The interview transcripts were analysed through content analysis. The study was approved by the Regional Ethics Review Board (reference number: 2015/4).ResultsThe analysis resulted in the identification of three main thematic categories: The unavoidable and unknown end of life, Thoughts on control and Living your last period of life at a nursing home. The older persons did not fear death itself but had some worries about dying. Spending the last stage of life at a nursing home contributed to different thoughts and feelings among the older persons. With a few exceptions, older persons characterized life at the nursing home as boring and felt they were surrounded by people who did not belong there.ConclusionsThis study indicates a need for older persons to talk about death, dying and end-life issues. Furthermore, this study highlighted that the co-residence of cognitively healthy persons and persons with dementia in the same ward adversely affected cognitively healthy persons. This situation resulted in there being not enough time to both handle the care needs of persons with dementia and have the conversations that cognitively healthy persons desired, such as conversations about thoughts about existence, that could have improved their quality of life.
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| 9. |
- Wanngren, Johanna, et al.
(författare)
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Changed membrane integration and catalytic site conformation are two mechanisms behind the increased Aβ42/Aβ40 ratio by presenilin 1 familial Alzheimer-linked mutations.
- 2014
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Ingår i: FEBS Open Bio. - : Wiley. - 2211-5463. ; 4, s. 393-406
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Tidskriftsartikel (refereegranskat)abstract
- The enzyme complex γ-secretase generates amyloid β-peptide (Aβ), a 37-43-residue peptide associated with Alzheimer disease (AD). Mutations in presenilin 1 (PS1), the catalytical subunit of γ-secretase, result in familial AD (FAD). A unifying theme among FAD mutations is an alteration in the ratio Aβ species produced (the Aβ42/Aβ40 ratio), but the molecular mechanisms responsible remain elusive. In this report we have studied the impact of several different PS1 FAD mutations on the integration of selected PS1 transmembrane domains and on PS1 active site conformation, and whether any effects translate to a particular amyloid precursor protein (APP) processing phenotype. Most mutations studied caused an increase in the Aβ42/Aβ40 ratio, but via different mechanisms. The mutations that caused a particular large increase in the Aβ42/Aβ40 ratio did also display an impaired APP intracellular domain (AICD) formation and a lower total Aβ production. Interestingly, seven mutations close to the catalytic site caused a severely impaired integration of proximal transmembrane/hydrophobic sequences into the membrane. This structural defect did not correlate to a particular APP processing phenotype. Six selected FAD mutations, all of which exhibited different APP processing profiles and impact on PS1 transmembrane domain integration, were found to display an altered active site conformation. Combined, our data suggest that FAD mutations affect the PS1 structure and active site differently, resulting in several complex APP processing phenotypes, where the most aggressive mutations in terms of increased Aβ42/Aβ40 ratio are associated with a decrease in total γ-secretase activity.
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