| 1. |
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| 2. |
- Sen, P, et al.
(författare)
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Vaccine hesitancy decreases in rheumatic diseases, long-term concerns remain in myositis: a comparative analysis of the COVAD surveys
- 2023
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Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 62:10, s. 3291-3301
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveCOVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys.MethodsThe first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups.ResultsWe analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P < 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P < 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P < 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs – OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs – OR: 5.4 95% CI: 3, 9.6, P < 0.001). Caucasians [OR 4.2 (1.7–10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8–0.97)].ConclusionVaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.
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| 3. |
- Barregård, Lars, 1948, et al.
(författare)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 4. |
- Abellán, C., et al.
(författare)
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Challenging Local Realism with Human Choices
- 2018
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 557, s. 212-216
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Tidskriftsartikel (refereegranskat)abstract
- A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bi-partite and tri-partite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.
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| 5. |
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| 6. |
- Rudke, A. P., et al.
(författare)
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Landscape changes over 30 years of intense economic activity in the upper Paraná River basin
- 2022
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Ingår i: Ecological Informatics. - : Elsevier BV. - 1574-9541. ; 72
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we show the complexity associated with the recent land cover changes by elucidating the paths of 30 years of changes in the Upper Paraná River Basin (UPRB), a region severely impacted by agricultural activity, one of the areas with the highest density in the production of hydroelectricity, biofuels and food in the world. In this sense, a post-classification comparison approach based on Landsat images was used to identify detailed ‘from-to’ paths behind those land cover changes. The most expressive changes were the expansion of Cropland and Forest areas and the reduction in savannas, with a net change of 17.9%, 4.1%, and −16.9% of the UPRB area, respectively. Cropland areas showed an expressive increase between 1985 and 2015, rising from 249,439 km2 (27.7%) to 412,909 km2 (45.9%). Forest areas increased from 149,389 km2 to 185,839 km2 in the period. Notably, for this class, an intense spatial dynamic of losses (7.5%) and gains (11.6%) took place between 1985 and 2015. This behavior is related to the disappearance of native vegetation fragments in some sub-basins, as well as to afforestation, reforestation, and/or forest restoration in others. The Cerrado (a typical tropical savanna in South America), the most impacted natural biome of the Basin, decreased from 21.9% of the UPRB in 1985 (196,746 km2) to only about 5% of the whole UPRB area in 2015. Grassland areas, mostly used for livestock, decreased from 271,827 km2 (30.2%) to 229,007 km2 (25.5%). This net decrease was associated with a reduction of 160,830 km2 (17.8%) and the appearance of 118,010 km2 (13.2%) in new areas, previously occupied by tropical savannas in 1985. In conclusion, economic factors were the main drivers for land cover changes, especially agriculture and livestock activities, besides forestry and hydroelectric energy production. In addition, Grassland areas that predominated on the left banks of the UPRB in 1985 retreated with the advance of Cropland areas, mainly due to the expansion of sugarcane for ethanol production, a biofuel widely used in Brazil. In turn, pasture areas migrated to the right bank and occupied a significant part of the Cerrado. Finally, our results demonstrate that the transition dynamics among land cover classes can involve complex political-economical mechanisms that are not always captured by remote sensing.
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| 7. |
- Andreoli, L., et al.
(författare)
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COVID-19 VACCINE SAFETY DURING PREGNANCY AND BREASTFEEDING IN WOMEN WITH AUTOIMMUNE DISEASES : RESULTS FROM THE COVAD STUDY
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 56-57
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: COVID-19 vaccine hesitancy among pregnant and breastfeeding women with autoimmune diseases (AID) is often attributed to the fear of adverse events (AE) and disease flares (DF). No data are available regarding COVID-19 vaccine safety in this population.Objectives: We aimed at describing delayed-onset (>7 days) vaccine-related AE (minor and major), DF, and related AID treatment modifications from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study.Methods: Among complete responses from 9201 participants as of June 21, 2022, 6787 (73.8%) were women. Six subgroups were identified upon diagnosis of AID vs healthy controls (HC) and their pregnancy/breastfeeding status at the time of any dose of vaccine (Figure 1).Results: Forty pregnant and 52 breastfeeding AID patients were identified and their vaccination rates (at least one dose) was 100% and 96.2%, respectively (Table 1). Overall AE, minor AE, and major AE were reported significantly more frequently by pregnant than non-pregnant patients (45% vs. 26%, p=0.01; 40% vs. 25.9%, p=0.03; 17.5% vs. 4.6%, p<0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC. Post-vaccination DF were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18% of age- and disease-matched control patients (n=2315). All DF in pregnant/breastfeeding patients were managed with glucocorticoids and a fifth of them required initiation or change in immunosuppressive treatment.Conclusion: This study provides the first insights into the safety of COVID-19 vaccination during the antenatal period in women with AID. While AEs were more commonly reported by pregnant patients with AID, these were no higher than among pregnant healthy controls without AID. These observations are reassuring, likely to strengthen physician-patient communication and overcome hesitancy as the benefits for the mother and fetus by passive immunization are likely to overweigh the potential risks of AE and DF.Reference: [1]Fazal ZZ, et al; COVAD Study Group. COVAD survey 2 long-term outcomes: unmet need and protocol. Rheumatol Int 2022; 42:2151-2158.
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| 8. |
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| 9. |
- Andreoli, L, et al.
(författare)
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EULAR recommendations for women's health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome
- 2017
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 76:3, s. 476-485
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Tidskriftsartikel (refereegranskat)abstract
- Develop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).MethodsSystematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus.ResultsFamily planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease.ConclusionsRecommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.
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| 10. |
- Bianchi, F., et al.
(författare)
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Novel sample-substrates for the determination of new psychoactive substances in oral fluid by desorption electrospray ionization-high resolution mass spectrometry
- 2019
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Ingår i: Talanta. - : Elsevier B.V.. - 0039-9140 .- 1873-3573. ; 202, s. 136-144
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Tidskriftsartikel (refereegranskat)abstract
- A reliable screening and non invasive method based on the use of microextraction by packed sorbent coupled with desorption electrospray ionization-high resolution mass spectrometry was developed and validated for the detection of new psychoactive substances in oral fluid. The role of different sample substrates in enhancing signal intensity and stability was evaluated by testing the performances of two polylactide-based materials, i.e. non-functionalized and functionalized with carbon nanoparticles, and a silica-based material compared to commercially available polytetrafluorethylene supports. The best results were achieved by using the non-functionalized polylactide substrates to efficiently ionize compounds in positive ionization mode, whereas the silica coating proved to be the best choice for operating in negative ionization mode. LLOQs in the low μg/L, a good precision with CV% always lower than 16% and RR% in the 83(±4)-120(±2)% range, proved the suitability of the developed method for the determination of the analytes in oral fluid. Finally, the method was applied for screening oral fluid samples for the presence of psychoactive substances during private parties, revealing mephedrone in only one sample out of 40 submitted to analysis.
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| 11. |
- Jeliazkova, N, et al.
(författare)
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Towards FAIR nanosafety data
- 2021
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Ingår i: Nature nanotechnology. - : Springer Science and Business Media LLC. - 1748-3395 .- 1748-3387. ; 16:86, s. 644-
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Tidskriftsartikel (refereegranskat)
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| 12. |
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| 13. |
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| 14. |
- Tektonidou, MG, et al.
(författare)
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EULAR recommendations for the management of antiphospholipid syndrome in adults
- 2019
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Ingår i: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:10, s. 1296-1304
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2–3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2–3 or INR 3–4 is recommended, considering the individual’s bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3–4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.
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| 18. |
- Chertow, GM, et al.
(författare)
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Study Design and Baseline Characteristics of the CARDINAL Trial: A Phase 3 Study of Bardoxolone Methyl in Patients with Alport Syndrome
- 2021
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 52:3, s. 180-189
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Introduction:</i></b> Alport syndrome is a rare genetic disorder that affects as many as 60,000 persons in the USA and a total of 103,000 persons (<5 per 10,000) in the European Union [1, 2]. It is the second most common inherited cause of kidney failure and is characterized by progressive loss of kidney function that often leads to end-stage kidney disease. Currently, there are no approved disease-specific agents for therapeutic use. We designed a phase 3 study (CARDINAL; NCT03019185) to evaluate the safety, tolerability, and efficacy of bardoxolone methyl in patients with Alport syndrome. <b><i>Methods:</i></b> The CARDINAL phase 3 study is an international, multicenter, double-blind, placebo-controlled, randomized registrational trial. Eligible patients were of ages 12–70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR 30–90 mL/min/1.73 m<sup>2</sup>, and urinary albumin to creatinine ratio (UACR) ≤3,500 mg/g. Patients with B-type natriuretic peptide values >200 pg/mL at baseline or with significant cardiovascular histories were excluded. Patients were randomized 1:1 to bardoxolone methyl or placebo, with stratification by baseline UACR. <b><i>Results:</i></b> A total of 371 patients were screened, and 157 patients were randomly assigned to receive bardoxolone methyl (<i>n</i> = 77) or placebo (<i>n</i> = 80). The average age at screening was 39.2 years, and 23 (15%) were <18 years of age. Of the randomized population, 146 (93%) had confirmed genetic diagnosis of Alport syndrome, and 62% of patients had X-linked mode of inheritance. Mean baseline eGFR was 62.7 mL/min/1.73 m<sup>2</sup>, and the geometric mean UACR was 141.0 mg/g. The average annual rate of eGFR decline prior to enrollment in the study was −4.9 mL/min/1.73 m<sup>2</sup> despite 78% of the patient population receiving ACE inhibitor (ACEi) or ARB therapy. <b><i>Discussion/Conclusion:</i></b> CARDINAL is one of the largest interventional, randomized controlled trials in Alport syndrome conducted to date. Despite the use of ACEi or ARB, patients were experiencing significant loss of kidney function prior to study entry.
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| 19. |
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| 20. |
- Gennari, R, et al.
(författare)
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Early detection of cancer: ideas for a debate.
- 2007
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Ingår i: critical reviews in Oncology Hematology. - : Elsevier BV. - 1040-8428. ; 61, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- Even if the overall number of cancer is increasing, the mortality has started to decrease in the Western World. The role of early detection in this decrease is a matter of debate. To assess its impact on mortality it is important to distinguish between diagnosis of cancer in symptomatic patients, and early detection in asymptomatic individuals who may self-refer or who may be offered ad hoc or systematic screening. The policies for early detection and screening vary greatly between European countries, despite many similarities in their cancer burden, and this partly reflects the uncertainties surrounding asymptomatic testing for cancer. A Task Force of European expert, held in Azzate (VA), Italy, established to address these issues, acknowledged the need for more research in the field of individual risk assessment since general statistics are more and more perceived as inadequate to design personal early detection plans. The group also recognised that combinations of early detection and screening will enforce the effectiveness of new treatments in curbing mortality curves, although policies will vary with different cancers.
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| 21. |
- Giannopoulou, N., et al.
(författare)
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COVID-19 VACCINE SAFETY DURING PREGNANCY IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS
- 2023
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Ingår i: Annals of the Rheumatic Diseases. - : HighWire Press. - 0003-4967 .- 1468-2060. ; 82:Suppl. 1, s. 1495-1496
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Vaccinations comprise a part of the antenatal care of pregnant women, including patients with systemic lupus erythematosus (SLE) who are at increased risk of adverse pregnancy outcomes (APOs). While COVID-19 vaccination has been shown to be safe in patients with SLE, data on vaccine-associated adverse events (AEs) during the antenatal and lactation period are scarce or lacking.Objectives: To investigate the association between COVID-19 vaccination and AEs in pregnant SLE patients.Methods: A total of 9201 complete responses were extracted on June 21st, 2022 from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) 2 database, a global e-survey involving 157 collaborators from 106 countries. Among respondents, 6787 (73.8%) were women. We identified 70 (1.1%) women who were exposed to at least one COVID-19 vaccine dose during pregnancy, among those 11 with SLE. Delayed onset (>7 days) vaccine-related AEs were extracted and triangulated with disease activity, treatment changes due to flare after vaccination, and COVID-19 infections in vaccinated pregnant women with SLE. Additionally, information on health-related quality of life and physical function was recorded using PROMIS at the time of survey completion.Results: The age of patients ranged from 28 to 39 years; 5/11 women were of Asian origin. None of these patients reported major vaccine AEs, including four patients with self-reported active SLE prior to the vaccination. None of them reported any change in the status of their autoimmune disease, and no hospitalisation or special treatment was recorded. Six women experienced minor vaccine AEs; two of them had active disease prior to vaccination. Four patients reported COVID-19 infection; two of them while they were pregnant and post-vaccination and two prior to pregnancy and vaccination. All four patients experienced symptoms of their disease, but no overt SLE flare was reported. At the time of survey completion, all patients reported their general health as being good to excellent in all aspects evaluated. Importantly, no APOs were reported.None of the patients reported thrombotic events post-vaccination, which provides some reassurance regarding COVID-19 vaccination in a patient population with a high risk for cardiovascular comorbidity and thrombosis, especially in the presence of antiphospholipid antibodies or in patients diagnosed with the antiphospholipid syndrome, a considerable portion within SLE populations. Moreover, it was reassuring to note an absence of association between experienced vaccine AEs and active disease prior to vaccination. Although minor AEs were common, they did not impair daily functioning, and the symptoms resolved in all patients after a median of 3 (IQR: 2.5–5.0) days.Conclusion: Our report adds relevant evidence concerning the sensitive issue of COVID-19 vaccine AEs and flares in SLE patients during the antenatal and lactation period. Despite the small sample size, the findings provide some reassurance and can contribute to informed decisions regarding vaccination in patients with SLE and high-risk pregnancies due to their background autoimmune disease. Based on the present data, the risk/benefit ration of COVID-19 vaccination appears favourable, with vaccines both providing passive immunisation to the fetus and active immunisation to the mother with no signals of exacerbation of the mother’s autoimmune disease.
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