| 1. |
- Dolinska, Monika, et al.
(författare)
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Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option
- 2023
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
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Tidskriftsartikel (refereegranskat)abstract
- Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long -term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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| 2. |
- Jonsson, Ulf, et al.
(författare)
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Psychological Treatment of Depression in People Aged 65 Years and Over : A Systematic Review of Efficacy, Safety, and Cost-Effectiveness.
- 2016
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Depression in elderly people is a major public health concern. As response to antidepressants is often unsatisfactory in this age group, there is a need for evidence-based non-pharmacological treatment options. Our objectives were twofold: firstly, to synthesize published trials evaluating efficacy, safety and cost-effectiveness of psychological treatment of depression in the elderly and secondly, to assess the quality of evidence.METHOD: The electronic databases PubMed, EMBASE, Cochrane Library, CINAL, Scopus, and PsycINFO were searched up to 23 May 2016 for randomized controlled trials (RCTs) of psychological treatment for depressive disorders or depressive symptoms in people aged 65 years and over. Two reviewers independently assessed relevant studies for risk of bias. Where appropriate, the results were synthesized in meta-analyses. The quality of the evidence was graded according to GRADE (Grading of Recommendations Assessment, Development and Evaluation).RESULTS: Twenty-two relevant RCTs were identified, eight of which were excluded from the synthesis due to a high risk of bias. Of the remaining trials, six evaluated problem-solving therapy (PST), five evaluated other forms of cognitive behavioural therapy (CBT), and three evaluated life review/reminiscence therapy. In frail elderly with depressive symptoms, the evidence supported the efficacy of PST, with large but heterogeneous effect sizes compared with treatment as usual. The results for life-review/reminiscence therapy and CBT were also promising, but because of the limited number of trials the quality of evidence was rated as very low. Safety data were not reported in any included trial. The only identified cost-effectiveness study estimated an incremental cost per additional point reduction in Beck Depression Inventory II score for CBT compared with talking control and treatment as usual.CONCLUSION: Psychological treatment is a feasible option for frail elderly with depressive symptoms. However, important questions about efficacy, generalizability, safety and cost-effectiveness remain.
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| 3. |
- Tham, Anne, et al.
(författare)
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Efficacy and tolerability of antidepressants in people aged 65 years or older with major depressive disorder - A systematic review and a meta-analysis
- 2016
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Ingår i: Journal of Affective Disorders. - : Elsevier BV. - 0165-0327 .- 1573-2517. ; 205, s. 1-12
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Forskningsöversikt (refereegranskat)abstract
- Background: There has been a steady increase in the prescription of antidepressants for the elderly. This study comprises a systematic review of randomized, placebo-controlled trials of antidepressants for treatment of depressive disorder in people aged 65 years or more. Methods: PubMed, EMBASE, Cochrane Library, CINAL, and PsycINFO were searched until May 2016. Where appropriate, the results were synthesized in meta-analyses. Results: Twelve trials met the inclusion criteria. For patients with major depressive disorder, selective serotonin re-uptake inhibitors (SSRI) were not superior to placebo in achieving remission (OR: 0.79, 95% CI: 0.61-1.03) or response (OR=0.86, 95% CI: 0.51-1.10) after 8 weeks of treatment (three trials). However, maintenance treatment with SSRIs was superior to placebo in preventing relapse (OR: 0.22, 95% CI: 0.13-0.36; NNT=5, 95% CI: 3-6; two trials). Duloxetine was superior to placebo in achieving remission (OR: 1.78, 95% CI: 1.20-2.65; NNT=9, 95% CI: 6-20; three trials) and response (OR: 1.83, 95% CI: 1.96-4.08; two trials) in recurrent major depression after 8 weeks, but increased the risk of adverse events that can be problematic in the elderly. Limitations: The quality of evidence was generally low or moderate, emphasizing the uncertainty of the results. Study populations only partly covered the heterogeneous population of elderly with depressed mood, limiting the generalizability. Conclusion: The results underscore the importance of close monitoring of the effects of antidepressants in treatment of elderly patients with a depressive disorder. Methods for early detection of non-responders and effective treatment options for this group are needed.
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| 4. |
- Arkkukangas, Marina, et al.
(författare)
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A feasibility study of a randomised controlled trial comparing fall prevention using exercise with or without the support of motivational interviewing
- 2015
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Ingår i: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 2, s. 134-140
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this investigation was to study the feasibility of a randomised controlled trial (RCT) based on a multicentre fall prevention intervention including exercise with or without motivational interviewing compared to standard care in community-living people 75. years and older.Method: The feasibility of a three-armed, randomised controlled trial was evaluated according to the following: process, resources, management by questionnaire, and treatment outcomes. The outcome measures were fall frequency, physical performance and falls self-efficacy evaluated after three months. Twelve physiotherapists conducted the measurements and treatments and responded to the questionnaire. The first 45 participants recruited to the ongoing RCT were included: 16 individuals in the Otago Exercise Program group (OEP), 16 individuals in the OEP combined with motivational interviewing group (MI), and 13 individuals in the control group. The study was conducted from November 2012 to December 2013.Results: The feasibility of the study process, resources and management reached the set goals in most aspects; however, the set goal regarding the MI guide and planned exercise for the participating older people was not completely reached. No significant differences were found between the groups regarding the outcome measures.Conclusion: This study confirmed the acceptable feasibility for the study protocol in the ongoing RCT.
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| 5. |
- Arkkukangas, Marina, et al.
(författare)
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Fall Preventive Exercise With or Without Behavior Change Support for Community-Dwelling Older Adults : A Randomized Controlled Trial With Short-Term Follow-up
- 2019
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Ingår i: Journal of Geriatric Physical Therapy. - : Lippincott Williams & Wilkins. - 1539-8412 .- 2152-0895. ; 42:1, s. 9-17
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: In Western countries, falls and fall-related injuries are a well-known threat to health in the aging population. Studies indicate that regular exercise improves strength and balance and can therefore decrease the incidence of falls and fall-related injuries. The challenge, however, is to provide exercise programs that are safe, effective, and attractive to the older population. The aim of this study was to investigate the short-term effect of a home-based exercise program with or without motivational interviewing (MI) compared with standard care on physical performance, fall self-efficacy, balance, activity level, handgrip strength, adherence to the exercise, and fall frequency.Method: A total of 175 older adults participated in this randomized controlled study. They were randomly allocated for the Otago Exercise Program (OEP) (n = 61), OEP combined with MI (n = 58), or a control group (n = 56). The participants' mean age was 83 years. The recruitment period was from October 2012 to May 2015. Measurements of physical performance, fall self-efficacy, balance, activity level, handgrip strength, adherence to the exercise, and fall frequency were done before and 12 weeks after randomization.Results and Discussion: A total of 161 participants were followed up, and there were no significant differences between groups after a period of 12 weeks of regular exercise. Within the OEP + MI group, physical performance, fall self-efficacy, physical activity level, and handgrip strength improved significantly; likewise, improved physical performance and fall self-efficacy were found in the control group. A corresponding difference did not occur in the OEP group. Adherence to the exercise was generally high in both exercise groups.Conclusion: In the short-term perspective, there were no benefits of an exercise program with or without MI regarding physical performance, fall self-efficacy, activity level, handgrip strength, adherence to the exercise, and fall frequency in comparison to a control group. However, some small effects occurred within the OEP + MI group, indicating that there may be some possible value in behavioral change support combined with exercise in older adults that requires further evaluation in both short- and long-term studies.
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| 6. |
- Arkkukangas, Marina, et al.
(författare)
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Older persons' experiences of a home-based exercise program with behavioral change support
- 2017
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Ingår i: Physiotherapy Theory and Practice. - : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 33:12, s. 905-913
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is a challenge to promote exercise among older persons. Knowledge is needed regarding the maintenance of exercise aiming at preventing falls and promoting health and well-being in older persons.Purpose: This descriptive study used a qualitative inductive approach to describe older persons' experiences of a fall-preventive, home-based exercise program with support for behavioral change.Methods: Semi-structured interviews were conducted with 12 elderly persons aged 75years or older, and a qualitative content analysis was performed.Results: Four categories emerged: facilitators of performing exercise in everyday life, the importance of support, perceived gains from exercise, and the existential aspects of exercise.Conclusion: With support from physiotherapists (PTs), home-based exercise can be adapted to individual circumstances in a meaningful way. Including exercises in everyday life and daily routines could support the experience of being stronger, result in better physical functioning, and give hope for an extended active life in old age.
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| 7. |
- Arkkukangas, Marina, et al.
(författare)
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One-year adherence to the Otago Exercise Program with or without motivational interviewing in community-dwelling older adults
- 2018
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Ingår i: Journal of Aging and Physical Activity. - : Human Kinetics. - 1063-8652 .- 1543-267X. ; 26:3, s. 390-395
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Tidskriftsartikel (refereegranskat)abstract
- This study investigated if behavioral factors, treatment with behavioral support, readiness to change, fall self-efficacy, and activity habits could predict long-term adherence to an exercise program. Included in this study were 114 community-dwelling older adults who had participated in one of two home-based exercise interventions. Behavioral factors associated with adherence to the exercise program over 52 weeks were analyzed. The behavioral factors, specifically activity habits at baseline, significantly predicted adherence to the exercise program, with an odds ratio = 3.39, 95% confidence interval [1.38, 8.32], for exercise and an odds ratio = 6.11, 95% confidence interval [2.34, 15.94], for walks. Being allocated to a specific treatment including motivational interviewing was also significantly predictive: odds ratio = 2.47, 95% confidence interval [1.11, 5.49] for exercise adherence. In conclusion, activity habits and exercise in combination with motivational interviewing had a significant association with adherence to the exercise program at a 1-year follow-up.
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| 8. |
- Bring, Annika, 1967-
(författare)
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A Behavioural Medicine Perspective on Acute Whiplash Associated Disorders : Daily Coping, Prognostic Factors and Tailored Treatment
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to study the daily process of coping, potential prognostic factors for recovery and evaluating an individually tailored behavioural medicine intervention in the acute stage of Whiplash Associated Disorders (WAD). The studies comprised three samples of patients with acute Whiplash Associated Disorders (WAD). All patients were included within the first month after the whiplash occurrence and were recruited from hospital emergency wards in six Swedish communities.Study I and II included 51 participants generating 260 daily coping diaries (WAD-DCA) during seven days in the acute stage of WAD. In Study I daily stressors and primary appraisal were analysed and in Study II patterns between stressors, appraisals, coping strategy profiles, daily activity level and well-being were described. The results showed a large variety of situations that the individuals perceive as stressful, not only pain itself. High self-efficacy was associated with high degree of physical/mental well-being. Threatening stressors and catastrophic thoughts were associated with low degree of physical and mental well-being. In Study III potential prognostic factors for good as well as poor recovery were studied more closely in a mildly affected sample (MIAS) (n=98) from within the first month after the accident up to one year later. Pain-related disability at baseline emerged as the only indicator of prognosis after 12 months in MIAS. Study IV (n=55) was a randomised control study, were current clinical recommendations of standard self-care instructions (SC) for the management of acute WAD was compared to an individually tailored behavioural medicine intervention delivered via Internet or face-to-face. The results showed that SC was not as effective as the behavioural medicine intervention. By early identification of situation-specific factors and potential behavioural (physical, cognitive and affective) determinants of activity performance, it seems possible to tailor a self-management intervention that decreases pain-related disability, fear of movement and catastrophising and increases self-efficacy. The use of innovative methods such as the Internet of distributing treatment interventions showed to be a good alternative to more traditional forms.The results of this thesis uncover new insights in understanding the individual’s specific perspective as applied in a behavioural medicine approach in acute WAD.
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| 9. |
- Bring, Annika, et al.
(författare)
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Coping Patterns and Their Relation to Daily Activity, Worries, Depressed Mood, and Pain Intensity in Acute Whiplash-Associated Disorders
- 2013
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Ingår i: International Journal of Behavioral Medicine. - : Springer Science and Business Media LLC. - 1070-5503 .- 1532-7558. ; 20:2, s. 293-303
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDThere is a lack of knowledge regarding how individuals with acute whiplash-associated disorders (WAD) appraise and cope with situation-specific stressors.PURPOSEThe aim of the study was to describe the daily process of coping reported in a daily coping assessment by individuals with acute WAD within 1 month after the accident. More specifically, profiles of coping strategies were identified and patterns between stressors, primary and secondary appraisals, and coping strategy profiles were described in relation to reported level of activity, worries, depressed mood and pain intensity during the day.METHODA descriptive and exploratory design was applied. Two hundred and twenty-nine whiplash-associated disorders-daily coping assessment (WAD-DCA) collected during seven consecutive days from 51 participants with acute WAD in Sweden, were included. Cluster analysis was used to obtain coping strategy profiles and data were graphically visualised as patterns through the coping process.RESULTSWhen measuring coping as a daily process relating to the specific stressful situation, different coping pocess patterns appeared. During days with a high degree of physical and mental well-being, high self-efficacy beliefs seemed to be working as an important secondary appraisal, whereas during days with a low degree of physical and mental well-being primary appraisals of the stressor as a threat and catastrophic thoughts were present in the coping process.CONCLUSIONSEarly identification of situational- and individual-specific stressors, appraisals and coping efforts as measured by the WAD-DCA may contribute to the understanding of the coping process in the acute stage of WAD and its possible impact on recovery and adjustment.
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| 10. |
- Bring, Annika, et al.
(författare)
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Daily stressors in patients with acute whiplash associated disorders
- 2012
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Ingår i: Disability and Rehabilitation. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 34:21, s. 1783-1789
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stressors in acute whiplash associated disorders (WAD), as reported on a daily basis, have hitherto been neglected in research. The primary aim of this study was to describe the most stressful daily situation or event reported by individuals with acute WAD within a month of a whiplash trauma. Another aim was to describe the meaning and significance of these daily stressors, i.e. primary appraisal. Method: A descriptive design with a content analysis approach was used. 260 WAD-daily coping assessments (WAD-DCA) generated during 1 week by 51 participants with acute WAD were included in the study. Stressors were analysed using qualitative content analysis. Results: The reported stressors generated 13 categories covering a wide range of stressful situations in daily life related to (i) work, (ii) physical symptoms, (iii) feelings and cognitions, (iv) family and home responsibilities and (v) recreation. The majority of the stressors were appraised as "expected" as well as "disabling". Most threatening stressors were related to work, driving and feelings/cognitions. Conclusions: The wide variety of stressors indicates that it is not only pain itself that influences daily life in acute WAD. Early identification of individual and situation-specific stressors gives new data regarding what bothers individuals suffering from WAD after a collision and may be helpful in understanding the coping process in relation to specific stressors and stressor appraisals.
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