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- Anandavadivelan, P., et al.
(författare)
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Impact of weight loss and eating difficulties on health-related quality of life up to 10 years after oesophagectomy for cancer
- 2018
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Ingår i: British Journal of Surgery. - : WILEY. - 0007-1323 .- 1365-2168. ; 105:4, s. 410-418
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe weight loss is experienced by patients with eating difficulties after surgery for oesophageal cancer. The aim of this prospective cohort study was to asssess the influence of eating difficulties and severe weight loss on health-related quality of life (HRQoL) up to 10years after oesophagectomy.Methods: Data on bodyweight and HRQoL were collected at 6months, 3, 5 and 10years in patients who underwent surgery for oesophageal cancer in Sweden between 2001 and 2005. Exposures were percentage weight loss, and eating difficulties defined by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-OES18 questionnaire. Outcomes were HRQoL scores from the EORTC QLQ-C30 questionnaire. Repeated-measures ANOVA, adjusting for potential confounders, was used to assess the association between eating difficulties and weight loss (4 exposure groups) and HRQoL scores at each time point. Mean score differences (MDs) between time points or exposure groups were defined as clinically relevant in accordance with evidence-based interpretation guidelines.Results: In total, 92 of 104 10-year survivors (885 per cent) responded to the questionnaires. Weight loss was greatest within 6months of surgery. Patients with eating difficulties with or without weight loss reported clinically and statistically significantly worsened HRQoL in almost all aspects. The largest MD was seen between 5 and 10years after surgery for global quality of life, physical, role and social function (MD -22 to -30), as well for fatigue, nausea, dyspnoea, insomnia, appetite loss and diarrhoea (MD 24-36).Conclusion: Eating difficulties are associated with deterioration in several aspects of HRQoL up to 10years after surgery for oesophageal cancer.
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- Lindholm, L, et al.
(författare)
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Genetic re-targeting of adenovirus using a hyperstable scFv domain and an affibody (R) molecule against Her2/neu
- 2004
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 9, s. S250-S250
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Tidskriftsartikel (refereegranskat)abstract
- One important goal in gene therapy is to develop adenovirus (Ad) vectors that are genetically de-targeted as well as re-targeted. Genetic re-targeting of Ad using complex cell-binding ligands has previously not been possible. We have previously demonstrated that ligands for genetic re-targeting of adenoviruses must be able to fold correctly in the cytoplasm of virus producing cells, a milieu that is not conducive to the formation of disulphide bonds. Here, we describe functional Ad5 viruses with fibers and pIX capsid proteins genetically modified to contain two types of complex ligands. One is affibody® molecules, corresponding to small (6 kDa) binding proteins developed by combinatorial protein engineering using a single three-helix bundle staphylococcal protein A domain. The other type is hyperstable antibody scFv domains. The affibody molecule used here (ZH2N) is directed against Her2/neu. Recombinant viruses were constructed with ZH2N in three different positions: (i) at the C-terminus of shaft repeat 7 of de-knobbed fibers; (ii) at the C-terminus of pIX; and (iii) in the HI-loop of the fiber knob. Each of the viruses exhibited a characteristic phenotype regarding fiber content, growth and ability to infect Her2/neu expressing cells. In order to test the potentials of scFv liganded Ad vectors, a hyperstable antibody scFv against b-galactosidase was genetically incorporated into knobless fibers, in tandem with a mutated protein A domain reactive with IgG1 Fc that targeted the virus to Fc-expressing 293 cells. These fibers could be rescued into viable virions that retained the original antigen binding specificity of the scFv, demonstrating the basic potential of hyperstable scFvs for genetic re-targeting of Ad. Quite unexpectedly, the fiber content of Ad with knobless, scFv containing fibers was close to normal in contrast to other Ad with knobless fibers that generally has a much reduced fiber content. The hyperstable scFv was further fused to the C-terminus of the capsid protein pIX. The recombinant molecules could be rescued into viable viruses with wt fibers. The scFv retained its binding-specificity on the recombinant virions. The results demonstrate that, contrary to current beliefs, it is possible to construct Ad that genetically incorporates functional scFvs and other complex ligands into the virus fiber and pIX. The feasibility is demonstrated by the creation of different viruses that are re-targeted to Her2/neu. These viruses are currently in pre-clinical development.
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- Lundin, C., et al.
(författare)
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There is no association between combined oral hormonal contraceptives and depression : a Swedish register-based cohort study
- 2022
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Ingår i: British Journal of Obstetrics and Gynecology. - : John Wiley & Sons. - 1470-0328 .- 1471-0528. ; 129:6, s. 917-925
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether users of hormonal contraceptives (HCs) are at increased risk of depression compared with non-users. Design: Register-based cohort study.Setting: Sweden.Sample: Women aged 15–25 years between 2010 and 2017 with no prior antidepressant treatment, psychiatric diagnose or contraindication for HCs (n = 739 585).Methods: Women with a prescription of HC were identified via the Swedish Prescribed Drug Register (SPDR). Relative risks (RRs) for first depression diagnosis in current HC-users compared with non-users were modelled by Poisson regression. Adjustments included age, medical indication for HC-use and parental history of mental disorders, among others.Main outcome measures: Depression, captured by a redeemed prescription of antidepressant treatment, or a first depression diagnosis in the SPDR and the National Patient Register.Results: Compared with non-users, women on combined oral contraceptives (COCs) and oral progestogen-only products had lower or no increased risk of depression, relative risk (RR) 0.89 (95% CI 0.87–0.91) and 1.03 (95% CI 0.99–1.06) after adjustments, respectively. Age-stratified analyses demonstrated that COC use in adolescents conferred no increase in risk (RR 0.96, 95% CI 0.93–0.98), whereas use of progestogen-only pills (RR 1.13, 95% CI 1.07–1.19), contraceptive patch/vaginal ring (RR 1.43, 95% CI 1.30–1.58), implant (RR 1.38, 95% CI 1.30–1.45) or a levonorgestrel intrauterine device (RR 1.59, 95% CI 1.46–1.73) were associated with increased risks.Conclusions: This study did not find any association between use of COCs, which is the dominating HC in first time users, and depression. Non-oral products were associated with increased risks. Residual confounding must be addressed in the interpretation of the results. Tweetable abstract: There is no association between combined hormonal contraceptives and depression.
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