| 21. |
- Van Hemelrijck, M, et al.
(författare)
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Mortality following hip fractures in men with prostate cancer
- 2013
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Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 31:6
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- 49 Background: Rapid loss of bone-mineral density is a known side-effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). Hip fractures are also independently associated with risk of mortality. To our knowledge few population-based observational studies have yet investigated the risk of dying following fractures among men with PCa. We aimed to assess skeletal-related events and mortality in more detail by specifically studying the link between hip fractures in PCa men and risk of death. Methods: PCBaSe Sweden 2.0 is based on the National Prostate Cancer Register and contains age and county matched men free of PCa. We selected all men (n=14,205) who had been hospitalized with a hip fracture, as registered in the National Patient Register, between 2006 and 2010. A total of 2300 were diagnosed with PCa before the hip fracture and 66% of them were treated with ADT. The main outcome was death as registered in the National Cause of Death Register. The risk of death was estimated using multivariate Cox Proportional Hazards regression analyses and standardized mortality ratios (SMRs) taking into account PCa risk category, history of fractures, civil status, Charlson Comorbidity Index, and treatment with bisphosphonates. Results: In the analysis for risk of death >90 days after a hip fracture, there was an increased risk of death among PCa men on ADT, especially those aged <84 years (e.g., HR at 3-6 months after hip fracture: 2.47 (95%CI: 1.85-3.30) compared to men free of PCa with a hip fracture). The SMRs showed that PCa men on ADT who got a hip fracture were seven times more likely to die than expected in the reference population of all men with PCa, whereas PCa men who were not on ADT and had a hip fracture were 13 times more likely to die than expected in this reference population. However, the absolute risk difference between men with and without a hip fracture was 30 per 1,000 person-years when evaluating the effect of a hip fracturing among men on ADT, whereas a hip fracture would cause an additional 20 per 1,000 person-years to die among PCa men without ADT as well as among men free of PCa. Conclusions: Our SMRs and absolute risk calculations show that hip fractures are more dangerous in PCa men treated with ADT than in PCa men without ADT or in men free of PCa.
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| 22. |
- van Vollenhoven, R.F., et al.
(författare)
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Addition of infliximab compared with addition of sulfasalazine and hydroxychloroquine to methotrexate in patients with early rheumatoid arthritis (Swefot trial) : 1-year results of a randomised trial
- 2009
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 374:9688, s. 459-466
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Tidskriftsartikel (refereegranskat)abstract
- Background: New treatment strategies for early rheumatoid arthritis are evolving rapidly. We aimed to compare addition of conventional disease-modifying antirheumatic drugs (sulfasalazine and hydroxychloroquine) with addition of a tumour necrosis factor antagonist (infliximab) to methotrexate in patients with early rheumatoid arthritis. Methods: We undertook a randomised trial in 15 rheumatology units in Sweden. We enrolled patients with early rheumatoid arthritis (symptom duration less than1 year) and administered methotrexate (up to 20 mg per week). After 3-4 months, those who had not achieved low disease activity but who could tolerate methotrexate were randomly allocated by computer addition of either sulfasalazine and hydroxychloroquine or infliximab. Primary outcome was achievement of a good response according to European League Against Rheumatism (EULAR) criteria at 12 months. Patients were followed up to 24 months; here, we present findings at 12 months. Analysis was by intention to treat and we used non-responder imputation. The Swefot (Swedish Pharmacotherapy) study is registered in the WHO database at the Karolinska University Hospital, number CT20080004. Findings: 487 patients were initially enrolled. Of 258 who had not achieved low disease activity with methotrexate, 130 were allocated sulfasalazine and hydroxychloroquine and 128 were assigned infliximab. 32 of 130 (25%) patients allocated sulfasalazine and hydroxychloroquine achieved the primary outcome compared with 50 of 128 (39%) assigned infliximab (risk ratio 1·59 [95% CI 1·10-2·30], p=0·0160). Adverse events were balanced fairly well between the two groups and accorded with known adverse events of the drugs used. No deaths occurred in either group. Interpretation: In patients with early rheumatoid arthritis in whom methotrexate treatment failed, addition of a tumour necrosis factor antagonist to methotrexate monotherapy is clinically superior to addition of conventional disease-modifying antirheumatic drugs. Funding: Swedish Rheumatism Association, Schering-Plough.
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| 23. |
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| 24. |
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| 25. |
- Welen, Karin, et al.
(författare)
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COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial.
- 2021
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for SARS-CoV-2 host cell internalization.Hospitalised COVID-19 patients will be randomised (2:1) to enzalutamide plus standard of care vs. standard of care designed to identify superiority.Included participants, men or women above 50 years of age, must be hospitalised for PCR confirmed COVID-19 symptoms and not in need of immediate mechanical ventilation. Major exclusion criteria are breast-feeding or pregnant women, hormonal treatment for prostate or breast cancer, treatment with immunosuppressive drugs, current symptomatic unstable cardiovascular disease (see Additional file 1 for further details). The trial is registered at Umeå University Hospital, Region Västerbotten, Sweden and 8 hospitals are approved for inclusion in Sweden.Patients randomised to the treatment arm will be treated orally with 160 mg (4x40 mg) enzalutamide (Xtandi®) daily, for five consecutive days. The study is not placebo controlled. The comparator is standard of care treatment for patients hospitalised with COVID-19.The primary endpoints of the study are (time to) need of mechanical ventilation or discharge from hospital as assessed by a clinical 7-point ordinal scale (up to 30 days after inclusion).Randomisation was stratified by center and sex. Each strata was randomized separately with block size six with a 2:1 allocation ratio (enzalutamide + "standard of care": "standard of care"). The randomisation list, with consecutive subject numbers, was generated by an independent statistician using the PROC PLAN procedure of SAS version 9.4 software (SAS Institute, Inc, Cary, North Carolina) BLINDING (MASKING): This is an open-label trial.The trial is designed to have three phases. The first, an exploration phase of 45 participants (30 treatment and 15 control) will focus on safety and includes a more extensive laboratory assessment as well as more frequent safety evaluation. The second prolongation phase, includes the first 100 participants followed by an interim analysis to define the power of the study. The third phase is the continuation of the study up to maximum 600 participants included in total.The current protocol version is COVIDENZA v2.0 as of September 10, 2020. Recruitment started July 29, 2020 and is presently in safety pause after the first exploration phase. Recruitment is anticipated to be complete by 31 December 2021.Eudract number 2020-002027-10 ClinicalTrials.gov Identifier: NCT04475601 , registered June 8, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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