| 1. |
- Yildiz, B, et al.
(författare)
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Live well, die well - an international cohort study on experiences, concerns and preferences of patients in the last phase of life: the research protocol of the iLIVE study
- 2022
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Ingår i: BMJ OPEN. - : BMJ. - 2044-6055. ; 12:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Adequately addressing the needs of patients at the end of life and their relatives is pivotal in preventing unnecessary suffering and optimising their quality of life. The purpose of the iLIVE study is to contribute to high-quality personalised care at the end of life in different countries and cultures, by investigating the experiences, concerns, preferences and use of care of terminally ill patients and their families.Methods and analysisThe iLIVE study is an international cohort study in which patients with an estimated life expectancy of 6 months or less are followed up until they die. In total, 2200 patients will be included in 11 countries, that is, 200 per country. In addition, one relative per patient is invited to participate. All participants will be asked to fill in a questionnaire, at baseline and after 4 weeks. If a patient dies within 6 months of follow-up, the relative will be asked to fill in a post-bereavement questionnaire. Healthcare use in the last week of life will be evaluated as well; healthcare staff who attended the patient will be asked to fill in a brief questionnaire to evaluate the care that was provided. Qualitative interviews will be conducted with patients, relatives and healthcare professionals in all countries to gain more in-depth insights.Ethics and disseminationThe cohort study has been approved by ethics committees and the institutional review boards (IRBs) of participating institutes in all countries. Results will be disseminated through the project website, publications in scientific journals and at conferences. Within the project, there will be a working group focusing on enhancing the engagement of the community at large with the reality of death and dying.Trial registration numberNCT04271085.
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| 2. |
- Lundberg, C, et al.
(författare)
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Dementia and driving: an attempt at consensus
- 1997
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Ingår i: Alzheimer disease and associated disorders. - : Ovid Technologies (Wolters Kluwer Health). - 0893-0341. ; 11:1, s. 28-37
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Bozzola, Tiago, et al.
(författare)
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Sialic Acid Derivatives Inhibit SiaT Transporters and Delay Bacterial Growth
- 2022
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Ingår i: Acs Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 17:7, s. 1890-1900
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Tidskriftsartikel (refereegranskat)abstract
- Antibiotic resistance is a major worldwide concern, and new drugs with mechanistically novel modes of action are urgently needed. Here, we report the structure-based drug design, synthesis, and evaluation in vitro and in cellular systems of sialic acid derivatives able to inhibit the bacterial sialic acid symporter SiaT. We designed and synthesized 21 sialic acid derivatives and screened their affinity for SiaT by a thermal shift assay and elucidated the inhibitory mechanism through binding thermodynamics, computational methods, and inhibitory kinetic studies. The most potent compounds, which have a 180-fold higher affinity compared to the natural substrate, were tested in bacterial growth assays and indicate bacterial growth delay in methicillin-resistant Staphylococcus aureus. This study represents the first example and a promising lead in developing sialic acid uptake inhibitors as novel antibacterial agents.
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| 4. |
- Roseman, C., et al.
(författare)
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Persistent pain and its predictors after starting anti-tumour necrosis factor therapy in psoriatic arthritis : what is the role of inflammation control?
- 2023
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Ingår i: Scandinavian Journal of Rheumatology. - 0300-9742. ; 53:2, s. 94-103
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Tidskriftsartikel (refereegranskat)abstract
- Objective: While considerable focus has been placed on pain due to inflammation in psoriatic arthritis (PsA), less is reported on pain despite inflammation control. Here, we aimed to investigate the occurrence/predictors of persistent pain, including non-inflammatory components, after starting anti-tumour necrosis factor (anti-TNF) therapy. Method: Bionaïve PsA patients starting a first anti-TNF therapy 2004–2010 were identified (South Swedish Arthritis Treatment Group register; N = 351). Outcomes included unacceptable pain [visual analogue scale (VAS) pain > 40 mm], and unacceptable pain despite inflammation control (refractory pain; VAS pain > 40 mm + C-reactive protein < 10 mg/L + ≤ 1 swollen joint of 28), assessed at 0, 3, 6, and 12 months. Baseline predictors were estimated by logistic regression. Results: Upon starting anti-TNF therapy, 85% of patients reported unacceptable pain, falling to 43% at 3 months and then remaining stable. After 12 months, refractory pain constituted 63% of all unacceptable pain. Higher baseline VAS pain/global, worse physical function and lower health-related quality-of-life were associated with a higher risk of unacceptable/refractory pain at 12 months. More swollen joints and higher evaluator’s global assessment were associated with a lower risk of 12-month refractory pain. Conclusions: A substantial proportion of PsA patients reported unacceptable pain throughout the first anti-TNF treatment year. At 12 months, refractory pain constituted about two-thirds of this remaining pain load. More objective signs of inflammation at anti-TNF initiation were associated with less future refractory pain. This highlights insufficient effect of biologics in patients with inflammation-independent pain, warranting alternative treatments.
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| 5. |
- Andersson, Fredrik, 1977, et al.
(författare)
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Structure and function of a novel type of ATP-dependent Clp protease.
- 2009
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Ingår i: The Journal of biological chemistry. - 0021-9258 .- 1083-351X. ; 284:20, s. 13519-32
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Tidskriftsartikel (refereegranskat)abstract
- The Clp protease is conserved among eubacteria and most eukaryotes, and uses ATP to drive protein substrate unfolding and translocation into a chamber of sequestered proteolytic active sites. The main constitutive Clp protease in photosynthetic organisms has evolved into a functionally essential and structurally intricate enzyme. The model Clp protease from the cyanobacterium Synechococcus consists of the HSP100 molecular chaperone ClpC and a mixed proteolytic core comprised of two distinct subunits, ClpP3 and ClpR. We have purified the ClpP3/R complex, the first for a Clp proteolytic core comprised of heterologous subunits. The ClpP3/R complex has unique functional and structural features, consisting of twin heptameric rings each with an identical ClpP3(3)ClpR(4) configuration. As predicted by its lack of an obvious catalytic triad, the ClpR subunit is shown to be proteolytically inactive. Interestingly, extensive modification to ClpR to restore proteolytic activity to this subunit showed that its presence in the core complex is not rate-limiting for the overall proteolytic activity of the ClpCP3/R protease. Altogether, the ClpP3/R complex shows remarkable similarities to the 20 S core of the proteasome, revealing a far greater degree of convergent evolution than previously thought between the development of the Clp protease in photosynthetic organisms and that of the eukaryotic 26 S proteasome.
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| 6. |
- Aus, G, et al.
(författare)
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Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial
- 2002
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Ingår i: BJU International. - 1464-4096. ; 90:6, s. 561-566
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Tidskriftsartikel (refereegranskat)abstract
- Objective To describe the outcome, assessed as the level of prostate specific antigen (PSA), of a mature (more than half the events recorded) prospective randomized study with a median follow-up of 82 months of neoadjuvant hormonal therapy before radical prostatectomy, as this has been suggested to decrease the rate of positive surgical margins (i.e. provide greater potential to completely excise the tumour). Patient and methods From December 1991 to March 1994, 126 patients with clinically localized prostate cancer were randomized between direct radical prostatectomy or a 3-month course of a gonadotrophin-releasing hormone analogue before surgery. The patients were followed by PSA determinations and a value of > 0.5 ng/mL used to define progression. Results The incidence of positive surgical margins decreased from 45.5% to 23.6% (P = 0.016) with hormone treatment. Despite this there was no difference in PSA progression-free survival at the last follow-up; it was 51.5% for those undergoing radical prostatectomy only and 49.8% for those who received hormonal pretreatment (P = 0.588). Conclusions Three months of neoadjuvant hormonal therapy before radical prostatectomy offers no benefit to the patient and cannot be recommended for routine clinical use.
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| 7. |
- Bondesson, E., et al.
(författare)
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Comorbidity between pain and mental illness - Evidence of a bidirectional relationship
- 2018
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801. ; 22:7, s. 1304-1311
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pain from various locations in the body and mental illness are common and the comorbidity between the two is well-known although the temporal relationship remains to be determined. Our aim was to follow patients over time to study if pain (here dorsalgia/abdominal pain) or fibromyalgia lead to an increased risk of developing mental illness (here depression/anxiety) and/or the reverse, that is whether patients with mental illness have an increased risk to develop pain or fibromyalgia, compared to the rest of the population. Methods: This prospective cohort study used the Skåne Healthcare Register, covering all care in the region of Skåne, southern Sweden (population ~1.3 million). The cohort included healthcare consultations in primary care, outpatient specialized care and inpatient care between 2007 and 2016 for all patients without prior registered diagnosis of mental illness or pain, aged 18 or older (n = 504,365). Results: The incidence rate ratio (IRR) for developing mental illness after pain was 2.18 (95% CI = 2.14-2.22) compared to without pain. IRR for developing pain after mental illness was 2.02 (95% CI = 1.98-2.06) compared to without mental illness. Corresponding IRR for developing mental illness after fibromyalgia was 4.05 (95% CI = 3.58-4.59) and for developing fibromyalgia after mental illness 5.54 (95% CI = 4.99-6.16). Conclusions: This study shows a bidirectional influence of similar magnitude of pain and mental illness, respectively. In monitoring patients with pain or mental illness, a focus on both conditions is thus important to develop appropriate, targeted interventions and may increase the likelihood of improved outcomes. Significance: We followed a population-based cohort over a period of 10 years, including incident cases of both exposure and outcome and found a bidirectional relationship between pain and mental illness. Clinicians need to pay attention on both conditions, in patients seeking care due to mental illness or pain.
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| 8. |
- Bondesson, E, et al.
(författare)
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Consultation prevalence among children, adolescents and young adults with pain conditions : A description of age- And gender differences
- 2020
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 24:3, s. 649-658
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Pain is a common complaint presented in healthcare, but most epidemiological pain research has focused either on single pain conditions or on the adult population. The aim of this study was to investigate the 2017 consultation prevalence of a wide range of pain conditions in the general population of young people.METHODS: We used the Skåne Healthcare Register, covering prospectively collected data on all healthcare delivered (primary and secondary care) to the population in the region of Skåne, southern Sweden (population 2017 n = 1,344,689). For individuals aged 1-24 in 2017 (n = 373,178), we calculated the consultation prevalence, stratified by sex and age, and the standardised morbidity ratio (SMR) to assess overall healthcare consultation.RESULTS: A total of 58,981 (15.8%) individuals consulted at least once for any of the predefined pain conditions. Of these, 13.5% (n = 7,996) consulted four or more times for pain. Abdominal pain, joint pain/myalgia, headache and back/neck pain were the most common complaints. Overall, females had higher consultation prevalence than males: 17.6% versus 14.1% (p < .0001). SMR was 1.82 (95% CI = 1.74-1.87) for females with pain and 1.51 (95% CI = 1.42-1.56) for males with pain. Consultation prevalence increased with age, but this pattern varied between sex and pain condition.CONCLUSIONS: Among individuals under the age of 25, a significant proportion consult for pain already in early ages, and they also have high healthcare consultation rates for conditions other than pain. The even higher consultation rates among young females need additional attention, both in the clinic and in research.
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| 9. |
- Delcoigne, B, et al.
(författare)
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Feasibility of reusing time-matched controls in an overlapping cohort
- 2018
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Ingår i: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 27:6, s. 1818-1829
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Tidskriftsartikel (refereegranskat)abstract
- The methods developed for secondary analysis of nested case-control data have been illustrated only in simplified settings in a common cohort and have not found their way into biostatistical practice. This paper demonstrates the feasibility of reusing prior nested case-control data in a realistic setting where a new outcome is available in an overlapping cohort where no new controls were gathered and where all data have been anonymised. Using basic information about the background cohort and sampling criteria, the new cases and prior data are “aligned” to identify the common underlying study base. With this study base, a Kaplan–Meier table of the prior outcome extracts the risk sets required to calculate the weights to assign to the controls to remove the sampling bias. A weighted Cox regression, implemented in standard statistical software, provides unbiased hazard ratios. Using the method to compare cases of contralateral breast cancer to available controls from a prior study of metastases, we identified a multifocal tumor as a risk factor that has not been reported previously. We examine the sensitivity of the method to an imperfect weighting scheme and discuss its merits and pitfalls to provide guidance for its use in medical research studies.
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| 10. |
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