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- Schwille-Kiuntke, J., et al.
(författare)
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Postinfectious irritable bowel syndrome after travelers' diarrhea - a cohort study
- 2015
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 27:8, s. 1147-1155
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is sound evidence for the role of gastrointestinal infections in the development of postinfectious irritable bowel syndrome (PI-IBS), but understanding the interaction between mental factors and the infection remains incomplete. This study aims to (i) assess the occurrence of PI-IBS in a cohort of patients with self-reported travelers' diarrhea (TD), (ii) assess risk factors for PI-IBS development, and (iii) investigate the prognosis of PI-IBS after 1 year. Methods: Patients consulting the travel clinic at the University Hospital Tuebingen, Germany (in 2009 and 2010) were identified from records and questioned in follow-ups in 2011 and 2012. We used the Rome III modular questionnaire to assess IBS, the Hospital Anxiety and Depression Scale to assess anxiety and depression, and the Patient Health Questionnaire to assess somatization. Key Results: We identified 529 eligible subjects from the clinical records. Of 135 subjects (age: 36.6 ± 14.6 years, 58.5% female) included in the study sample 6.7% (95% CI 3.0-11.1) had PI-IBS. We found more females (88.9% vs 56.3%, p = 0.08) and younger age subjects (mean 29.3 vs 37.1 years, p = 0.02) among the PI-IBS subjects. A multivariable regression model revealed vomiting at baseline and high somatization scores as strong and independent PI-IBS risk factors. One year later PI-IBS occurrence decreased to 3.3% (three cases of 90). Conclusions & Inferences: Our findings underline the close linkage of mental and somatic processes for the manifestation of PI-IBS. Screening for psychiatric comorbidities in patients with severe gastrointestinal infections may allow identifying groups at high risk for PI-IBS.
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- Huttner, A., et al.
(författare)
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A dose-dependent plasma signature of the safety and immunogenicity of the rVSV-Ebola vaccine in Europe and Africa
- 2017
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Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 9:385
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Tidskriftsartikel (refereegranskat)abstract
- The 2014-2015 Ebola epidemic affected several African countries, claiming more than 11,000 lives and leaving thousands with ongoing sequelae. Safe and effective vaccines could prevent or limit future outbreaks. The recombinant vesicular stomatitis virus-vectored Zaire Ebola (rVSV-ZEBOV) vaccine has shown marked immunogenicity and efficacy in humans but is reactogenic at higher doses. To understand its effects, we examined plasma samples from 115 healthy volunteers from Geneva who received low-dose (LD) or high-dose (HD) vaccine or placebo. Fifteen plasma chemokines/cytokines were assessed at baseline and on days 1, 2 to 3, and 7 after injection. Significant increases in monocyte-mediated MCP-1/CCL2, MIP-1 beta/CCL4, IL-6, TNF-alpha, IL-1Ra, and IL-10 occurred on day 1. A signature explaining 68% of cytokine/chemokine vaccine-response variabilitywas identified. Its score was higher in HD versus LD vaccinees and was associated positively with vaccine viremia and negatively with cytopenia. It was higher in vaccinees with injection-site pain, fever, myalgia, chills, and headache; higher scores reflected increasing severity. In contrast, HD vaccinees who subsequently developed arthritis had lower day 1 scores than other HD vaccinees. Vaccine dose did not influence the signature despite its influence on specific outcomes. The Geneva-derived signature associated strongly (rho = 0.97) with that of a cohort of 75 vaccinees from a parallel trial in Lambarene, Gabon. Its score in Geneva HD vaccinees with subsequent arthritis was significantly lower than that in Lambarene HD vaccinees, none of whom experienced arthritis. This signature, which reveals monocytes' critical role in rVSV-ZEBOV immunogenicity and safety across doses and continents, should prove useful in assessments of other vaccines.
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- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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