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- Azzouzi, Abdel Rahmène, et al.
(författare)
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Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301) : An open-label, phase 3, randomised controlled trial
- 2017
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Ingår i: The Lancet Oncology. - 1470-2045. ; 18:2, s. 181-191
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and 2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. Methods: This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with . ClinicalTrials.gov, number . NCT01310894. Findings: Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24-25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24-0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53-5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3-4 adverse events were prostatitis (three [2%] in the vascular-targeted photodynamic therapy group . vs one [<1%] in the active surveillance group), acute urinary retention (three [2%] . vs one [<1%]) and erectile dysfunction (two [1%] . vs three [1%]). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). Interpretation: Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. Funding: Steba Biotech.
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- Bakari, Catherine, et al.
(författare)
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Trends of Plasmodium falciparum molecular markers associated with resistance to artemisinins and reduced susceptibility to lumefantrine in Mainland Tanzania from 2016 to 2021
- 2024
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Ingår i: MALARIA JOURNAL. - 1475-2875. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Therapeutic efficacy studies (TESs) and detection of molecular markers of drug resistance are recommended by the World Health Organization (WHO) to monitor the efficacy of artemisinin-based combination therapy (ACT). This study assessed the trends of molecular markers of artemisinin resistance and/or reduced susceptibility to lumefantrine using samples collected in TES conducted in Mainland Tanzania from 2016 to 2021. Methods A total of 2,015 samples were collected during TES of artemether-lumefantrine at eight sentinel sites (in Kigoma, Mbeya, Morogoro, Mtwara, Mwanza, Pwani, Tabora, and Tanga regions) between 2016 and 2021. Photo-induced electron transfer polymerase chain reaction (PET-PCR) was used to confirm presence of malaria parasites before capillary sequencing, which targeted two genes: Plasmodium falciparum kelch 13 propeller domain (k13) and P. falciparum multidrug resistance 1 (pfmdr1). Results Sequencing success was >= 87.8%, and 1,724/1,769 (97.5%) k13 wild-type samples were detected. Thirty-seven (2.1%) samples had synonymous mutations and only eight (0.4%) had non-synonymous mutations in the k13 gene; seven of these were not validated by the WHO as molecular markers of resistance. One sample from Morogoro in 2020 had a k13 R622I mutation, which is a validated marker of artemisinin partial resistance. For pfmdr1, all except two samples carried N86 (wild-type), while mutations at Y184F increased from 33.9% in 2016 to about 60.5% in 2021, and only four samples (0.2%) had D1246Y mutations. pfmdr1 haplotypes were reported in 1,711 samples, with 985 (57.6%) NYD, 720 (42.1%) NFD, and six (0.4%) carrying minor haplotypes (three with NYY, 0.2%; YFD in two, 0.1%; and NFY in one sample, 0.1%). Between 2016 and 2021, NYD decreased from 66.1% to 45.2%, while NFD increased from 38.5% to 54.7%. Conclusion This is the first report of the R622I (k13 validated mutation) in Tanzania. N86 and D1246 were nearly fixed, while increases in Y184F mutations and NFD haplotype were observed between 2016 and 2021. Despite the reports of artemisinin partial resistance in Rwanda and Uganda, this study did not report any other validated mutations in these study sites in Tanzania apart from R622I suggesting that intensified surveillance is urgently needed to monitor trends of drug resistance markers and their impact on the performance of ACT.
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- Barriere, Jerome, et al.
(författare)
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Scientific Integrity Requires Publishing Rebuttals and Retracting Problematic Papers
- 2023
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Ingår i: STEM CELL REVIEWS AND REPORTS. - : SPRINGER. - 2629-3269 .- 2629-3277. ; 19, s. 568-572
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Tidskriftsartikel (refereegranskat)abstract
- Recently, an article by Seneff et al. entitled "Innate immunosuppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs" was published in Food and Chemical Toxicology (FCT). Here, we describe why this article, which contains unsubstantiated claims and misunderstandings such as "billions of lives are potentially at risk" with COVID-19 mRNA vaccines, is problematic and should be retracted. We report here our request to the editor of FCT to have our rebuttal published, unfortunately rejected after three rounds of reviewing. Fighting the spread of false information requires enormous effort while receiving little or no credit for this necessary work, which often even ends up being threatened. This need for more scientific integrity is at the heart of our advocacy, and we call for large support, especially from editors and publishers, to fight more effectively against deadly disinformation.
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- Besancon, Lonni, et al.
(författare)
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Open science saves lives : lessons from the COVID-19 pandemic
- 2021
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Ingår i: BMC Medical Research Methodology. - : BMC. - 1471-2288. ; 21:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In the last decade Open Science principles have been successfully advocated for and are being slowly adopted in different research communities. In response to the COVID-19 pandemic many publishers and researchers have sped up their adoption of Open Science practices, sometimes embracing them fully and sometimes partially or in a sub-optimal manner. In this article, we express concerns about the violation of some of the Open Science principles and its potential impact on the quality of research output. We provide evidence of the misuses of these principles at different stages of the scientific process. We call for a wider adoption of Open Science practices in the hope that this work will encourage a broader endorsement of Open Science principles and serve as a reminder that science should always be a rigorous process, reliable and transparent, especially in the context of a pandemic where research findings are being translated into practice even more rapidly.
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- Frank, Fabrice, et al.
(författare)
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Raising concerns on questionable ethics approvals - a case study of 456 trials from the Institut Hospitalo-Universitaire Mediterranee Infection
- 2023
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Ingår i: RESEARCH INTEGRITY AND PEER REVIEW. - : BMC. - 2058-8615. ; 8:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background The practice of clinical research is strictly regulated by law. During submission and review processes, compliance of such research with the laws enforced in the country where it was conducted is not always correctly filled in by the authors or verified by the editors. Here, we report a case of a single institution for which one may find hundreds of publications with seemingly relevant ethical concerns, along with 10 months of follow-up through contacts with the editors of these articles. We thus argue for a stricter control of ethical authorization by scientific editors and we call on publishers to cooperate to this end. Methods We present an investigation of the ethics and legal aspects of 456 studies published by the IHU-MI (InstitutHospitalo-Universitaire Mediterranee Infection) in Marseille, France. Results We identified a wide range of issues with the stated research authorization and ethics of the published studies with respect to the Institutional Review Board and the approval presented. Among the studies investigated, 248 were conducted with the same ethics approval number, even though the subjects, samples, and countries of investigation were different. Thirty-nine (39) did not even contain a reference to the ethics approval number while they present research on human beings. We thus contacted the journals that published these articles and provide their responses to our concerns. It should be noted that, since our investigation and reporting to journals, PLOS has issued expressions of concerns for several publications we analyze here. Conclusion This case presents an investigation of the veracity of ethical approval,and more than 10 months of follow-up by independent researchers. We call forstricter control and cooperation in handling of these cases, including editorial requirement to upload ethical approval documents, guidelines from COPE to address such ethical concerns, and transparent editorial policies and timelines to answer such concerns. All supplementary materials are available.
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- Fälth, Billy, 1968-
(författare)
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Simulating Earthquake Rupture and Near-Fault Fracture Response
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Sweden is presently a low seismicity area where most earthquakes are small and pose no serious threat to constructions. For the long-term perspectives of safety assessments of geological repositories for spent nuclear fuel, however, the effects of large earthquakes have to be considered. For the Swedish nuclear waste storage concept, seismically induced secondary fracture shear displacements across waste canister positions could pose a long-term seismic risk to the repository.In this thesis, I present earthquake simulations with which I study the potential for near-fault secondary fracture shear displacements. As a measure I use the Coulomb Failure Stress (CFS), but also calculate explicit fracture displacements. I account for both the dynamic and quasi-static stress perturbations generated during the earthquake. As numerical tool I use the 3DEC code, whose performance I validate using Stokes closed-form solution and the Compsyn code as benchmarks. In a model of a Mw 6.4 earthquake, I investigate how fault roughness, the fault rupture propagation model and rupture velocity may impact the near-fault CFS evolution. I find that fault roughness can reduce the amount of fault slip by tens of percent, but also increase the near-fault CFS with similar amounts locally. Furthermore, different fault rupture models generate similar CFS levels. I also find that the secondary stresses scale with rupture velocity.In a model based on data from the Forsmark nuclear waste repository site, and assuming stress conditions prevailing at the end of a glaciation, I simulate several high stress drop ~Mw 5.6 earthquake scenarios on the gently dipping fault zone ZFMA2 and calculate secondary fracture displacements on 300 m diameter planar fractures. Less than 1% of the fractures at the shortest distance from ZFMA2 generate displacements exceeding the 50 mm criterion established by the Swedish Nuclear Fuel and Waste Management Co. Given the high stress drops and the assumption of fracture planarity, I consider the calculated displacements to represent upper bound estimates of possible secondary displacements at Forsmark. Hence, the results should strengthen the confidence in the safety assessment of the nuclear waste repository at the Forsmark site.
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