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Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]

BACKGROUND: Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol) led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect. METHODS: Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter. RESULTS: No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3°C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 °C). Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period. CONCLUSIONS: Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome

Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]

BACKGROUND: Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol) led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect. METHODS: Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter. RESULTS: No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3°C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 °C). Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period. CONCLUSIONS: Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome

Correction: PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN74418480]

BACKGROUND: The Paracetamol (Acetaminophen) In Stroke (PAIS) study is a phase III multicenter, double blind, randomized, placebo-controlled clinical trial of high-dose acetaminophen in patients with acute stroke. The trial compares treatment with a daily dose of 6 g acetaminophen, started within 12 hours after the onset of symptoms, with matched placebo. The purpose of this study is to assess whether treatment with acetaminophen for 3 days will result in improved functional outcome through a modest reduction in body temperature and prevention of fever.The previously planned statistical analysis based on a dichotomization of the scores on the modified Rankin Scale (mRS) may not make the most efficient use of the available baseline information. Therefore, the planned primary analysis of the PAIS study has been changed from fixed dichotomization of the mRS to a sliding dichotomy analysis. METHODS: Instead of taking a single definition of good outcome for all patients, the definition is tailored to each individual patient's baseline prognosis on entry into the trial. CONCLUSION: The protocol change was initiated becau

Electron-phonon interaction in C70

The matrix elements of the deformation potential of C$_{70}$ are calculated by means of a simple, yet accurate solution of the electron-phonon coupling problem in fullerenes, based on a parametrization of the ground state electronic density of the system in terms of $sp^{2+x}$ hybridized orbitals. The value of the calculated dimensionless total electron-phonon coupling constant is $\lambda\approx0.1$, an order of magnitude smaller than in C$_{60}$, consistent with the lack of a superconducting phase transition in C$_{70}$A$_3$ fullerite, and in overall agreement with measurements of the broadening of Raman peaks in C$_{70}$K$_4$. We also calculate the photoemission cross section of C$_{70}^-$, which is found to display less structure than that associated with C$_{60}^-$, in overall agreement with the experimental findings.Comment: To be published in Phys. Rev.

PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN 74418480]

BACKGROUND: In patients with acute stroke, increased body temperature is associated with large lesion volumes, high case fatality, and poor functional outcome. A 1°C increase in body temperature may double the odds of poor outcome. Two randomized double-blind clinical trials in patients with acute ischemic stroke have shown that treatment with a daily dose of 6 g acetaminophen (paracetamol) results in a small but rapid and potentially worthwhile reduction of 0.3°C (95% CI: 0.1–0.5) in body temperature. We set out to test the hypothesis that early antipyretic therapy reduces the risk of death or dependency in patients with acute stroke, even if they are normothermic. METHODS/DESIGN: Paracetamol (Acetaminophen) In Stroke (PAIS) is a randomized, double-blind clinical trial, comparing high-dose acetaminophen with placebo in 2500 patients. Inclusion criteria are a clinical diagnosis of hemorrhagic or ischemic stroke and the possibility to start treatment within 12 hours from onset of symptoms. The study will have a power of 86% to detect an absolute difference of 6% in the risk of death or dependency at three months, and a power of 72% to detect an absolute difference of 5%, at a 5% significance level. DISCUSSION: This is a simple trial, with a drug that only has a small effect on body temperature in normothermic patients. However, when lowering body temperature with acetaminophen does have the expected effectiveness, 20 patients will have to be treated to prevent dependency or death in one

Omental infarction in the postpartum period: a case report and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Omental infarction is a rare and often misdiagnosed clinical event with unspecific symptoms. It affects predominantly young and middle aged women.</p> <p>Case presentation</p> <p>This is a case report of a 26-year-old Caucasian woman with spontaneous omental infarction two weeks after normal vaginal delivery.</p> <p>Conclusion</p> <p>Omental infarction is a differential diagnosis in the postpartum acute abdomen. As some cases of omental infarction, which are caused by torsion, can be adequately diagnosed via computed tomography, a conservative treatment strategy for patients without complications should be considered in order to avoid any unnecessary surgical intervention.</p

Active surveillance in renal transplant patients with prostate cancer: a multicentre analysis

Introduction: Due to medical improvements leading to increased life expectancy after renal transplantation and widened eligibility criteria allowing older patients to be transplanted, incidence of (low-risk) prostate cancer (PCa) is increasing among renal transplant recipients (RTR). It remains to be established whether active surveillance (AS) for PCa represents a safe treatment option in this setting. Therefore, we aim to compare AS discontinuation and oncological outcomes of AS for PCa of RTR vs. non-transplant patients. Methods: Multicentre study including RTR diagnosed with PCa between 2008 and 2018 in whom AS was initiated. A subgroup of non-RTR from the St. Antonius hospital AS cohort was used as a control group. Comparison of RTR vs. non-RTR was performed by 2:1 propensity score matched survival analysis. Outcome measures included tumour progression-free survival, treatment-free survival, metastasis rates, biochemical recurrence rates and overall survival. Patients were matched based on age, year of diagnosis, PSA, biopsy ISUP grade group, relative number of positive biopsy cores and clinical stage. Results: A total of 628 patients under AS were evaluated, including 17 RTRs and 611 non-RTRs. A total of 13 RTR cases were matched with 24 non-RTR cases. Median overall follow-up for the RTR and non-RTR matched cases was, respectively, 5.1 (IQR 3.2–8.7) years and 5.7 (IQR 4.8–8.1) years. There were no events of metastasis and biochemical recurrence among matched cases. The matched-pair analysis results in a 1-year and 5-year survival of the RTR and non-RTR patients were, respectively, 100 vs. 92%, and 39 vs. 76% for tumour progression, 100 vs. 91% and 59 vs. 76% for treatment-free survival and, respectively, 100 vs. 100% and 88 vs. 100% for overall survival. No significant differences in tumour progression-free survival (p = 0.07) and treatment-free survival were observed (p = 0.3). However, there was a significant difference in overall survival comparing both groups (p = 0.046). Conclusions: AS may be carefully considered in RTR with low-risk PCa. In our preliminary analysis, no major differences were present in AS outcomes between RTR and non-RTR. Overall mortality was significantly higher in the RTR subgroup

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure