| 1. |
- Gimsing, Peter, et al.
(författare)
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Effect of pamidronate 30 mg versus 90 mg on physical function in patients with newly diagnosed multiple myeloma (Nordic Myeloma Study Group): a double-blind, randomised controlled trial
- 2010
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Ingår i: LANCET ONCOLOGY. - : Elsevier Science B.V., Amsterdam.. - 1470-2045 .- 1474-5488. ; 11:10, s. 973-982
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Tidskriftsartikel (refereegranskat)abstract
- Background Compared with placebo, prophylactic treatment with bisphosphonates reduces risk of skeletal events in patients with multiple myeloma. However, because of toxicity associated with long-term bisphosphonate treatment, establishing the lowest effective dose is important. This study compared the effect of two doses of pamidronate on health-related quality of life and skeletal morbidity in patients with newly diagnosed multiple myeloma. Methods This double-blind, randomised, phase 3 trial was undertaken at 37 clinics in Denmark, Norway, and Sweden. Patients with multiple myeloma who were starting antimyeloma treatment were randomly assigned in a 1:1 ratio to receive one of two doses of pamidronate (30 mg or 90 mg) given by intravenous infusion once a month for at least 3 years. Randomisation was done by use of a central, computerised minimisation system. Primary outcome was physical function after 12 months estimated by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire (scale 0-100). All patients who returned questionnaires at 12 months and were still on study treatment were included in the analysis of the primary endpoint. This study is registered with ClinicalTrials. gov, number NCT00376883. Findings From January, 2001, until August, 2005, 504 patients were randomly assigned to pamidronate 30 mg or 90 mg (252 in each group). 157 patients in the 90 mg group and 156 in the 30 mg group were included in the primary analysis. Mean physical function at 12 months was 66 points (95% CI 62.9-70.0) in the 90 mg group and 68 points (64.6-71.4) in the 30 mg group (95% CI of difference -6.6 to 3.3; p=0.52). Median time to first skeletal-related event in patients who had such an event was 9.2 months (8.1-10.7) in the 90 mg group and 10-2 months (7.3-14.0) in the 30 mg group (p=0.63). In a retrospective analysis, eight patients in the pamidronate 90 mg group developed osteonecrosis of the jaw compared with two patients in the 30 mg group. Interpretation Monthly infusion of pamidronate 30 mg should be the recommended dose for prevention of bone disease in patients with multiple myeloma.
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| 2. |
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| 3. |
- Blimark, Cecilie, et al.
(författare)
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Melphalan 100mg/m(2) with stem cell support as first relapse treatment is safe and effective for myeloma patients with long remission after autologous stem cell transplantation.
- 2011
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Ingår i: European journal of haematology. - : Wiley. - 1600-0609 .- 0902-4441. ; 87:2, s. 117-22
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Today, a number of therapeutic options are available as the patient with myeloma relapses from initial treatment with high-dose melphalan and autologous stem cell transplantation (ASCT). For patients who experience a durable response to primary ASCT, retreatment with high-dose melphalan is recommended by many current guidelines. Yet, toxicity is an important aspect in the choice of relapse treatment, and a second ASCT in this setting could be associated with enhanced toxicity. As the goal for the treatment for relapsed myeloma should be disease control while maintaining quality of life, lower doses of melphalan might be preferable. Methods and Objectives: In this retrospective study, we account for the outcome of 66 patients with myeloma in first systemic relapse after ASCT, who were treated with intermediate-dose melphalan, 100mg/m(2) , and stem cell support (MEL 100). The aim was to evaluate this treatment in relation to prior response duration after initial ASCT and with respect to response rate, toxicity and survival. Results: The overall response rate was 62%. There was limited, mostly haematological, toxicity, and no treatment-related mortality was observed. The median progression-free survival (PFS) was 8.5months, and the median overall survival was 24months. Patients with time to progression of 34months or more (n=17; ≥75th percentile) after initial ASCT had a median PFS of 12.5months after MEL 100. Conclusion: For patients with a long-lasting response after ASCT, MEL 100 could be a therapeutic option with low toxicity and with efficacy comparable to newer immunomodulatory drugs.
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| 4. |
- Hjorth, Martin, et al.
(författare)
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Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma: a randomized study.
- 2012
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Ingår i: European journal of haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 88:6, s. 485-496
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives. Methods: Thalidomide- and bortezomib-naïve patients with melphalan refractory myeloma were randomly assigned to low-dose thalidomide + dexamethasone (Thal-Dex) or bortezomib + dexamethasone (Bort-Dex). At progression on either therapy, the patients were offered crossover to the alternative drug combination. An estimated 300 patients would be needed for the trial to detect a 50% difference in median PFS between the treatment arms. Results: After inclusion of 131 patients, the trial was prematurely closed because of low accrual. Sixty-seven patients were randomized to Thal-Dex and 64 to Bort-Dex. Progression-free survival was similar (median, 9.0 months for Thal-Dex and 7.2 for Bort-Dex). Response rate was similar (55% for Thal-Dex and 63% for Bort-Dex), but time to response was shorter (P < 0.05) and the VGPR rate higher (P < 0.01) for Bort-Dex. Time-to-other treatment after crossover was similar (median, 13.2 months for Thal-Dex and 11.2 months for Bort-Dex), as was overall survival (22.8 months for Thal-Dex and 19.0 for Bort-Dex). Venous thromboembolism was seen in seven patients and cerebrovascular events in four patients in the Thal-Dex group. Severe neuropathy, reactivation of herpes virus infections, and mental depression were more frequently observed in the Bort-Dex group. In the quality-of-life analysis, no difference was noted for physical function, pain, and global quality of life. Fatigue and sleep disturbances were significantly more prevalent in the Bort-Dex group. Conclusions: Thalidomide (50–100 mg daily) in combination with dexamethasone seems to have an efficacy comparable with that of bortezomib and dexamethasone in melphalan refractory myeloma. However, the statistical strength of the results in this study is limited by the low number of included patients.
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| 5. |
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| 6. |
- Kann, D. A., et al.
(författare)
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THE AFTERGLOWS OF SWIFT-ERA GAMMA-RAY BURSTS. I. COMPARING PRE-SWIFT AND SWIFT-ERA LONG/SOFT (TYPE II) GRB OPTICAL AFTERGLOWS
- 2010
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 720:2, s. 1513-1558
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Tidskriftsartikel (refereegranskat)abstract
- We have gathered optical photometry data from the literature on a large sample of Swift-era gamma-ray burst (GRB) afterglows including GRBs up to 2009 September, for a total of 76 GRBs, and present an additional three pre-Swift GRBs not included in an earlier sample. Furthermore, we publish 840 additional new photometry data points on a total of 42 GRB afterglows, including large data sets for GRBs 050319, 050408, 050802, 050820A, 050922C, 060418, 080413A, and 080810. We analyzed the light curves of all GRBs in the sample and derived spectral energy distributions for the sample with the best data quality, allowing us to estimate the host-galaxy extinction. We transformed the afterglow light curves into an extinction-corrected z = 1 system and compared their luminosities with a sample of pre-Swift afterglows. The results of a former study, which showed that GRB afterglows clustered and exhibited a bimodal distribution in luminosity space, are weakened by the larger sample. We found that the luminosity distribution of the two afterglow samples (Swift-era and pre-Swift) is very similar, and that a subsample for which we were not able to estimate the extinction, which is fainter than the main sample, can be explained by assuming a moderate amount of line-of-sight host extinction. We derived bolometric isotropic energies for all GRBs in our sample, and found only a tentative correlation between the prompt energy release and the optical afterglow luminosity at 1 day after the GRB in the z = 1 system. A comparative study of the optical luminosities of GRB afterglows with echelle spectra (which show a high number of foreground absorbing systems) and those without, reveals no indication that the former are statistically significantly more luminous. Furthermore, we propose the existence of an upper ceiling on afterglow luminosities and study the luminosity distribution at early times, which was not accessible before the advent of the Swift satellite. Most GRBs feature afterglows that are dominated by the forward shock from early times on. Finally, we present the first indications of a class of long GRBs, which form a bridge between the typical high-luminosity, high-redshift events and nearby low-luminosity events (which are also associated with spectroscopic supernovae) in terms of energetics and observed redshift distribution, indicating a continuous distribution overall.
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| 7. |
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| 8. |
- Margutti, R., et al.
(författare)
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A PANCHROMATIC VIEW OF THE RESTLESS SN 2009ip REVEALS THE EXPLOSIVE EJECTION OF A MASSIVE STAR ENVELOPE
- 2014
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 780:1
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Tidskriftsartikel (refereegranskat)abstract
- The double explosion of SN 2009ip in 2012 raises questions about our understanding of the late stages of massive star evolution. Here we present a comprehensive study of SN 2009ip during its remarkable rebrightenings. High-cadence photometric and spectroscopic observations from the GeV to the radio band obtained from a variety of ground-based and space facilities (including the Very Large Array, Swift, Fermi, Hubble Space Telescope, and XMM) constrain SN 2009ip to be a low energy (E similar to 1050 erg for an ejecta mass similar to 0.5 M-circle dot) and asymmetric explosion in a complex medium shaped by multiple eruptions of the restless progenitor star. Most of the energy is radiated as a result of the shock breaking out through a dense shell of material located at similar to 5 x 10(14) cm with M similar to 0.1 M-circle dot, ejected by the precursor outburst similar to 40 days before the major explosion. We interpret the NIR excess of emission as signature of material located further out, the origin of which has to be connected with documented mass-loss episodes in the previous years. Our modeling predicts bright neutrino emission associated with the shock break-out if the cosmic-ray energy is comparable to the radiated energy. We connect this phenomenology with the explosive ejection of the outer layers of the massive progenitor star, which later interacted with material deposited in the surroundings by previous eruptions. Future observations will reveal if the massive luminous progenitor star survived. Irrespective of whether the explosion was terminal, SN 2009ip brought to light the existence of new channels for sustained episodic mass loss, the physical origin of which has yet to be identified.
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| 9. |
- Schulze, S., et al.
(författare)
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GRB 120422A/SN 2012bz : Bridging the gap between low- and high-luminosity gamma-ray bursts
- 2014
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 566
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Tidskriftsartikel (refereegranskat)abstract
- Context. At low redshift, a handful of gamma-ray bursts (GRBs) have been discovered with luminosities that are substantially lower (L-iso less than or similar to 10(48.5) erg s(-1)) than the average of more distant ones (L-iso greater than or similar to 10(49.5) erg s(-1)). It has been suggested that the properties of several low-luminosity (low-L) GRBs are due to shock break-out, as opposed to the emission from ultrarelativistic jets. This has led to much debate about how the populations are connected. Aims. The burst at redshift z = 0.283 from 2012 April 22 is one of the very few examples of intermediate-L GRBs with a gamma-ray luminosity of L-iso similar to 10(49.6-49.9) erg s(-1) that have been detected up to now. With the robust detection of its accompanying supernova SN 2012bz, it has the potential to answer important questions on the origin of low-and high-L GRBs and the GRB-SN connection. Methods. We carried out a spectroscopy campaign using medium-and low-resolution spectrographs with 6-10-m class telescopes, which covered a time span of 37.3 days, and a multi-wavelength imaging campaign, which ranged from radio to X-ray energies over a duration of similar to 270 days. Furthermore, we used a tuneable filter that is centred at H alpha to map star-formation in the host and the surrounding galaxies. We used these data to extract and model the properties of different radiation components and fitted the spectral energy distribution to extract the properties of the host galaxy. Results. Modelling the light curve and spectral energy distribution from the radio to the X-rays revealed that the blast wave expanded with an initial Lorentz factor of Gamma(0) similar to 50, which is a low value in comparison to high-L GRBs, and that the afterglow had an exceptionally low peak luminosity density of less than or similar to 2 x 10(30) erg s(-1) Hz(-1) in the sub-mm. Because of the weak afterglow component, we were able to recover the signature of a shock break-out in an event that was not a genuine low-L GRB for the first time. At 1.4 hr after the burst, the stellar envelope had a blackbody temperature of k(B)T similar to 16 eV and a radius of similar to 7 x 10(13) cm (both in the observer frame). The accompanying SN 2012bz reached a peak luminosity of M-V = -19.7 mag, which is 0.3 mag more luminous than SN 1998bw. The synthesised nickel mass of 0.58 M-circle dot, ejecta mass of 5.87 M-circle dot, and kinetic energy of 4.10x10(52) erg were among the highest for GRB-SNe, which makes it the most luminous spectroscopically confirmed SN to date. Nebular emission lines at the GRB location were visible, which extend from the galaxy nucleus to the explosion site. The host and the explosion site had close-to-solar metallicity. The burst occurred in an isolated star-forming region with an SFR that is 1/10 of that in the galaxy's nucleus. Conclusions. While the prompt gamma-ray emission points to a high-L GRB, the weak afterglow and the low Gamma(0) were very atypical for such a burst. Moreover, the detection of the shock break-out signature is a new quality for high-L GRBs. So far, shock break-outs were exclusively detected for low-L GRBs, while GRB 120422A had an intermediate L-iso of similar to 10(49.6-49.9) erg s(-1). Therefore, we conclude that GRB 120422A was a transition object between low-and high-L GRBs, which supports the failed-jet model that connects low-L GRBs that are driven by shock break-outs and high-L GRBs that are powered by ultra-relativistic jets.
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| 10. |
- Ulleryd, Peter, 1958, et al.
(författare)
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Legionnaires' disease from a cooling tower in a community outbreak in Lidkoping, Sweden-epidemiological, environmental and microbiological investigation supported by meteorological modelling
- 2012
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 12, s. 313-
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Tidskriftsartikel (refereegranskat)abstract
- Background: An outbreak of Legionnaires' Disease took place in the Swedish town Lidkoping on Lake Vanern in August 2004 and the number of pneumonia cases at the local hospital increased markedly. As soon as the first patients were diagnosed, health care providers were informed and an outbreak investigation was launched. Methods: Classical epidemiological investigation, diagnostic tests, environmental analyses, epidemiological typing and meteorological methods. Results: Thirty-two cases were found. The median age was 62 years (range 36 - 88) and 22 (69%) were males. No common indoor exposure was found. Legionella pneumophila serogroup 1 was found at two industries, each with two cooling towers. In one cooling tower exceptionally high concentrations, 1.2 x 10(9) cfu/L, were found. Smaller amounts were also found in the other tower of the first industry and in one tower of the second plant. Sero-and genotyping of isolated L. pneumophila serogroup 1 from three patients and epidemiologically suspected environmental strains supported the cooling tower with the high concentration as the source. In all, two L. pneumophila strains were isolated from three culture confirmed cases and both these strains were detected in the cooling tower, but one strain in another cooling tower as well. Meteorological modelling demonstrated probable spread from the most suspected cooling tower towards the town centre and the precise location of four cases that were stray visitors to Lidkoping. Conclusions: Classical epidemiological, environmental and microbiological investigation of an LD outbreak can be supported by meteorological modelling methods. The broad competence and cooperation capabilities in the investigation team from different authorities were of paramount importance in stopping this outbreak.
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