| 1. |
- Yildiz, B, et al.
(author)
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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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In: BMJ OPEN. - : BMJ. - 2044-6055. ; 12:8
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Journal article (other academic/artistic)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. |
- Bozzola, Tiago, et al.
(author)
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Sialic Acid Derivatives Inhibit SiaT Transporters and Delay Bacterial Growth
- 2022
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In: Acs Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 17:7, s. 1890-1900
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Journal article (peer-reviewed)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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| 3. |
- Roseman, C., et al.
(author)
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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?
- 2024
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In: Scandinavian Journal of Rheumatology. - 0300-9742 .- 1502-7732. ; 53:2, s. 94-103
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Journal article (peer-reviewed)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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| 4. |
- Schelin, S, et al.
(author)
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Feedback microwave thermotherapy versus TURP/prostate enucleation surgery in patients with benign prostatic hyperplasia and persistent urinary retention : A prospective, randomized, controlled, multicenter study
- 2006
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In: Urology. - : Elsevier BV. - 0090-4295 .- 1527-9995. ; 68:4, s. 795-799
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Journal article (peer-reviewed)abstract
- Objectives: To assess the clinical efficacy of ProstaLund Feedback Treatment (PLFT) using the CoreTherm device versus transurethral resection of the prostate (TURP) and prostate enucleation surgery. Methods: We performed a prospective, randomized, controlled, multicenter study of 120 patients with symptomatic benign prostatic hyperplasia and persistent urinary retention requiring an indwelling catheter or clean intermittent catheterization. The primary efficacy variables were success in catheter removal and symptom improvement. Results: Of the 120 patients, 79% and 88% were catheter free after PLFT and surgery, respectively. The bother score (quality-of-life question) decreased from 4.6 in both groups before treatment to 1.4 in the PLFT group and 0.8 in the surgery group at 6 months of follow-up. The peak urinary flow rate was 13.4 mL/s after PLFT and 18.0 mL/s after surgery. The mean catheterization time was 34 days in the PLFT group and 5 days in the surgery group. Conclusions: PLFT is an effective alternative to surgical treatment in this group of catheterized patients. The risk of severe complications is reduced using PLFT, and an excellent treatment option can thereby be offered to this high-risk patient group who earlier could be treated only with lifelong catheterization. © 2006 Elsevier Inc. All rights reserved.
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| 5. |
- Wagrell, L, et al.
(author)
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Feedback microwave thermotherapy versus TURP for clinical BPH - A randomized controlled multicenter study
- 2002
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In: Urology. - 1527-9995. ; 60:2, s. 292-299
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Journal article (peer-reviewed)abstract
- Objectives. To compare the outcome of a microwave thermotherapy feedback system that is based on intraprostatic temperature measurement during treatment (ProstaLund Feedback Treatment or PLFT) with transurethral resection of the prostate (TURP) for clinical benign prostatic hyperplasia (BPH) in a randomized controlled multicenter study. The safety of the two methods was also investigated. Methods. The study was performed at 10 centers in Scandinavia and the United States. A total of 154 patients with clinical BPH were randomized to PLFT or TURP (ratio 2:1); 133 of them completed the study and were evaluated at the end of the study 12 months after treatment. Outcome measures included the International Prostate Symptom Score (IPSS), urinary flow, detrusor pressure at maximal urinary flow (Qmax), prostate volume, and adverse events. Patients were seen at 3, 6, and 12 months. Responders were defined according to a combination of IPSS and Qmax: IPSS 7 or less, or a minimal 50% gain, and/or Qmax 15 mL/s or greater or a minimal 50% gain. Results. No significant differences in outcome at 12 months were found between PLFT and TURP for IPSS, Qmax, or detrusor pressure. The prostate volume measured with transrectal ultrasonography was reduced by 30% after PLFT and 51% after TURP. Serious adverse events related to the given treatment were reported in 2% after PLFT and in 17% after TURP. Mild and moderate adverse events were more common in the PLFT group. With the criteria mentioned above, 82% and 86% of the patients were characterized as responders after 12 months in the PLFT and TURP groups, respectively. The post-treatment catheter time was 3 days in the TURP group and 14 days in the PLFT group. Conclusions. The outcome of microwave thermotherapy with intraprostatic temperature monitoring was comparable with that seen after TURP in this study. From both a simplicity and safety point of view, PLFT appears to have an advantage. Taken together, our findings make us conclude that: within a 1-year perspective microwave thermotherapy with PLFT is an attractive alternative to TURP in the treatment of BPH.
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| 6. |
- Wagrell, L, et al.
(author)
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Three-year follow-up of feedback microwave thermotherapy versus TURP for clinical BPH: A prospective randomized multicenter study
- 2004
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In: Urology. - : Elsevier BV. - 1527-9995 .- 0090-4295. ; 64:4, s. 698-702
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Journal article (peer-reviewed)abstract
- Objectives. To compare, in a prospective randomized multicenter study, the efficacy and safety of transurethral microwave thermotherapy with Prostalund Feedback Treatment (PLFT), using the CoreTherm device, with transurethral resection of the prostate (TURP) 36 months after treatment. Methods. The study was conducted at 10 centers in the United States and Scandinavia. A total of 154 patients with benign prostatic hyperplasia were randomized to PLFT or TURP in a 2:1 ratio. The treatment outcome was evaluated on the basis of the International Prostate Symptom Score (IPSS), the quality-of-life question (QOL) of the IPSS, peak urinary flow rate (Qmax), urodynamics, and adverse events. The microwave power and treatment time were adjusted according to each patient's response to the supplied energy (ie, the intraprostatic temperature guided the PLFT). Results. Statistically significant improvements in both the TURP and the PLFT groups were observed for IPSS, QOL, and Qmax at 36 months. The average value for the PLFT group was 8.2, 1.2, and 11.9 mL/s for IPSS, QOL, and Qmax, respectively. The corresponding values for the TURP group were IPSS 5.0, QOL 1.0, and Qmax 13.5 mUs. The difference in IPSS outcome was statistically significant; however, no statistically significant differences were found in QOL or Qmax between the two treatment groups. The degree of improvement was in the same range as that observed after 12 and 24 months for both groups. During the 12 to 36-month period, the most frequent adverse events in the TURP group were impotence (15%), micturition urgency (13%), and urethral disorder (8%); in the PLFT group, impotence (8%), prostate-specific antigen increase (5%), and hematuria (4%) were the most common. Conclusions. The clinical outcome 3 years after microwave thermotherapy with PLFT was comparable to the results seen after TURP. The safety of PLFT compared favorably to that of TURP in this study.
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| 7. |
- Schelin, M. E.C., et al.
(author)
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Widespread non-joint pain in early rheumatoid arthritis
- 2021
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 50:4, s. 271-279
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Journal article (peer-reviewed)abstract
- Objective: The aim of the study was to assess the development of widespread non-joint pain (WNP) in a cohort of patients with early rheumatoid arthritis (RA), the associated health-related quality of life (HRQoL), and clinical and demographic risk factors for WNP. Method: Incident cases with RA, from the Swedish population-based study Epidemiological Investigation of Rheumatoid Arthritis (EIRA), with a follow-up of at least 3 years, constituted the study population. WNP was defined as pain outside the joints in all four body quadrants and was assessed at the 3 year follow-up. Patients who reported WNP were compared to patients without WNP regarding HRQoL, measured by the Short Form-36, at 3 years, and clinical and demographic characteristics at the time of RA diagnosis. Results: A total of 749 patients constituted the study sample, of whom 25 were excluded after reporting already having severe pain before RA diagnosis. At the 3 year follow-up, 8% of the patients reported having WNP as well as statistically significant worse HRQoL. At the time of RA diagnosis, the patients with WNP had worse pain and pain-related features, while no difference was seen in the inflammatory parameters. Conclusion: WNP occurs in a substantial subset of patients with RA, also early in the course of the disease, and the HRQoL for these patients is significantly reduced. Patients who develop WNP at 3 years are already distinguishable at the time of diagnosis by displaying more pronounced pain ratings together with an average level of inflammatory disease activity.
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| 8. |
- Aus, G, et al.
(author)
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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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In: BJU International. - 1464-4096. ; 90:6, s. 561-566
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Journal article (peer-reviewed)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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| 9. |
- Barker-Astrom, K., et al.
(author)
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Chlorosis during nitrogen starvation is altered by carbon dioxide and temperature status and is mediated by the ClpP1 protease in Synechococcus elongatus
- 2005
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In: Archives of Microbiology. - : Springer Science and Business Media LLC. - 0302-8933 .- 1432-072X. ; 183:1, s. 66-69
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Journal article (peer-reviewed)abstract
- The interactive effects of inorganic carbon status, temperature and light on chlorosis induced by nitrogen deficiency, and the roles of Clp proteases in this process were investigated. In wild-type cultures grown in high or ambient CO2, following transfer to media lacking combined nitrogen, phycocyanin per cell dropped primarily through dilution of the pigment through cell division, and also suffered variable degrees of net degradation. When grown at high CO2 (5%), chlorophyll (Chl) suffered net degradation to a greater extent than phycocyanin. In marked contrast, growth at ambient CO2 resulted in Chl per cell dropping through dilution. Conditions that drove net Chl degradation in the wild-type resulted in little or no net Chl degradation in a clpPI inactivation mutant, with Chl content dropping largely through growth dilution in the mutant. The chlorotic response of a clpPII inactivation strain was nearly the same as that of wild-type, although phycocyanin degradation may have been slightly accelerated in the former.
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| 10. |
- Delcoigne, B, et al.
(author)
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Feasibility of reusing time-matched controls in an overlapping cohort
- 2018
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In: Statistical methods in medical research. - : SAGE Publications. - 1477-0334 .- 0962-2802. ; 27:6, s. 1818-1829
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Journal article (peer-reviewed)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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