10 research outputs found

    Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients : A Randomized Controlled Trial

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    BACKGROUND: Efavirenz is well known for its clinical cognitive side-effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing Efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing Efavirenz. SETTING: a randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug- versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes. METHODS: virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA. RESULTS: 14 control and 34 switch subjects completed the study. There were no differences at baseline. Group-analysis demonstrated a significantly better improvement for the switch group on the domains attention (p=0.041) and speed of information processing (p=0.014). Normative comparison analyses showed that 5 out of the 34 patients who switched (15%) improved on NPA-score as compared to the control group. Interestingly, subjective improvement after discontinuing Efavirenz made 74% of the switch group chose for a regime without Efavirenz after study completion. CONCLUSION: switching from Atripla to Eviplera resulted in objective cognitive improvement on group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients that would benefit from discontinuing Efavirenz

    Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients : A Randomized Controlled Trial

    No full text
    Background:Efavirenz is well known for its clinical cognitive side effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing efavirenz.Setting:A randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes.Methods:Virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA.Results:Fourteen control and 34 switch subjects completed the study. There were no differences at baseline. Group analysis demonstrated a significantly better improvement for the switch group on the domains attention (P = 0.041) and speed of information processing (P = 0.014). Normative comparison analyses showed that 5 of the 34 patients who switched (15%) improved on NPA score as compared to the control group. Interestingly, subjective improvement after discontinuing efavirenz made 74% of the switch group chose for a regime without efavirenz after study completion.Conclusions:Switching from Atripla to Eviplera resulted in objective cognitive improvement on the group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients who would benefit from discontinuing efavirenz

    Objective and Subjective Improvement of Cognition After Discontinuing Efavirenz in Asymptomatic Patients : A Randomized Controlled Trial

    No full text
    BACKGROUND: Efavirenz is well known for its clinical cognitive side-effects. Even asymptomatic patients who switch for other reasons than neurocognitive complaints have reported a subjective improvement in cognitive functioning after discontinuing Efavirenz. The aim of this study was to assess the effect on cognition of switching Atripla (TDF/FTC/EFV) to Eviplera (TDF/FTC/RPV), hypothesizing an improvement when discontinuing Efavirenz. SETTING: a randomized controlled design with a highly comparable comparator drug was used to minimize bias and to differentiate drug- versus learning effects. An extensive sensitive neuropsychological assessment (NPA) was used to detect subtle changes. METHODS: virologically suppressed, cognitively asymptomatic male HIV-infected patients on Atripla were included and randomized (2:1) to switch to Eviplera (switch group) or continue on Atripla (control group) for 12 weeks. At baseline and week 12, patients underwent an extensive NPA. RESULTS: 14 control and 34 switch subjects completed the study. There were no differences at baseline. Group-analysis demonstrated a significantly better improvement for the switch group on the domains attention (p=0.041) and speed of information processing (p=0.014). Normative comparison analyses showed that 5 out of the 34 patients who switched (15%) improved on NPA-score as compared to the control group. Interestingly, subjective improvement after discontinuing Efavirenz made 74% of the switch group chose for a regime without Efavirenz after study completion. CONCLUSION: switching from Atripla to Eviplera resulted in objective cognitive improvement on group level in cognitively asymptomatic patients. Discrepancies in objective and subjective cognitive complaints make it challenging to identify patients that would benefit from discontinuing Efavirenz

    Association of reperfusion with brain edema in patients with acute ischemic stroke: A secondary analysis of the MR CLEAN Trial

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    IMPORTANCE: It is uncertain whether therapeutic reperfusion with endovascular treatment yields more or less brain edema. OBJECTIVE To elucidate the association between reperfusion and brain edema. The secondary objectives were to evaluate whether brain edema could partially be responsible for worse outcomes in patients with later reperfusion or lower Alberta Stroke Program Early Computed Tomography Score. DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), which was a prospective, randomized, multicenter clinical trial of endovascular treatment compared with conventional care of patients with acute anterior circulation ischemic stroke. Of 502 patients enrolled from December 2010 to June 2014, 2 patients declined to participate. Additionally, exclusion criteria were absence of follow-up imaging or presence of parenchymal hematoma, resulting in 462 patients included in this study. Brain edema was assessed retrospectively, from December 10, 2016, to July 24, 2017, by measuring midline shift (MLS) in all available follow-up scans. Observers were blinded to clinical data. MAIN OUTCOMES AND MEASURES: Midline shift was assessed as present or absent and as a continuous variable. Reperfusion status was assessed by the modified thrombolysis in cerebral infarction score in the endovascular treatment arm. The modified arterial occlusive lesion score was used to evaluate the recanalization status in both arms. The modified Rankin scale score at 90 days was used for functional outcome. RESULTS Of 462 patients, the mean (SD) age was65 (11) years, and 41.8% (n = 193) were women. Successful reperfusion and recanalization were associated with a reduced likelihood of having MLS (adjusted common odds ratio, 0.25; 95% CI, 0.12-0.53; P < .001 and adjusted common odds ratio, 0.34; 95% CI, 0.21-0.55; P < .001, respectively). Midline shift was partially responsible for worse modified Rankin scale scores in patients without reperfusion or recanalization (MLS changed the logistic regression coefficients by 30.3% and 12.6%, respectively). In patients with delayed reperfusion or lower Alberta Stroke Program Early Computed Tomography Score, MLS mediated part of the worse modified Rankin scale scores, corresponding to a change in the regression coefficient of 33.3% and 64.2%, respectively. CONCLUSIONS AND RELEVANCE: Successful reperfusion was associated with reduced MLS. This study identifies an additional benefit of reperfusion in relation to edema, as well as rescuing ischemic brain tissue at risk for infarction

    Progression of liver fibrosis following acute hepatitis C virus infection in HIV-positive MSM

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    Background: Whether continued, accelerated liver fibrosis progression occurs following acute hepatitis C virus infection (AHCVI) in HIV-positive MSM is unknown. Design and methods: HIV-positive MSM from the AIDS Therapy Evaluation in the Netherlands and MSM Observational Study for Acute Infection with Hepatitis C-cohorts with primary AHCVI and at least one fibrosis-4 (FIB-4) measurement less than 2 years before and 1 year after estimated AHCVI were included. Mixed-effect linear models were used to evaluate (time-updated) determinants of FIB-4 levels over time. Determinants of transitioning to and from FIB-4 1.45 were examined using multistate Markov models. Results: Of 313 MSM, median FIB-4 measurements per individual was 12 (interquartile range = 8-18) and median follow-up following AHCVI was 3.5 years (interquartile range = 1.9-5.6). FIB-4 measurements averaged at 1.00 [95% confidence interval (CI) = 0.95-1.05] before AHCVI, 1.31 (95% CI = 1.25-1.38) during the first year of AHCVI and 1.10 (95% CI = 1.05-1.15) more than 1 year after AHCVI. Mean FIB-4 more than 1 year after AHCVI was higher for chronically infected patients compared with those successfully treated (P = 0.007). Overall FIB-4 scores were significantly higher with older age, lower CD4(+) cell count, longer duration from HIV-diagnosis or AHCVI, and nonresponse to HCV-treatment. At the end of follow-up, 60 (19.2%) and eight MSM (2.6%) had FIB-4 between 1.45-3.25 and >= 3.25, respectively. Older age, lower CD4(+) cell count and detectable HIV-RNA were significantly associated with higher rates of progression to FIB-4 > 1.45, whereas older age, longer duration from HIV-diagnosis and nonresponse to HCV-treatment were significantly associated with lower rates of regression to FIB-4 Conclusion: In this population of HIV-positive MSM, FIB-4 scores were higher during the first year of AHCVI, but FIB-4 >= 3.25 was uncommon by the end of follow-up. Well controlled HIV-infection appears to attenuate FIB-4 progression. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved

    Progression of liver fibrosis following acute hepatitis C virus infection in HIV-positive MSM

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    Molecular basis of virus replication, viral pathogenesis and antiviral strategie

    Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

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    Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons

    Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data

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