| 1. |
- Arora, Satish, et al.
(författare)
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Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate
- 2012
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier. - 1053-2498 .- 1557-3117. ; 31:3, s. 259-265
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (FIX) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. less thanbrgreater than less thanbrgreater thanMETHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediarninetetraacetic acid clearance. less thanbrgreater than less thanbrgreater thanRESULTS: In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((Delta mGFR 6.7 +/- 9.0 vs -1.6 +/- 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (Delta mGFR 5.1 +/- 11.1 vs -0.5 +/- 8.7 ml/min/1.73 m(2); p andlt; 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CM reduction during the study period. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.
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| 3. |
- Gullestad, Lars, et al.
(författare)
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Everolimus With Reduced Calcineurin Inhibitor in Thoracic Transplant Recipients With Renal Dysfunction: A Multicenter, Randomized Trial
- 2010
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Ingår i: Transplantation. - : Williams and Wilkins. - 0041-1337 .- 1534-6080. ; 89:7, s. 864-872
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Tidskriftsartikel (refereegranskat)abstract
- Background. The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. Methods. In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate greater than= 20 mL/min/1.73m(2) and less than90 mL/min/1.73 m(2)) greater than1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. Results. Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (Pless than0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). Conclusion. Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.
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| 4. |
- Gullestad, Lars, et al.
(författare)
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Two-Year Outcomes in Thoracic Transplant Recipients After Conversion to Everolimus With Reduced Calcineurin Inhibitor Within a Multicenter, Open-Label, Randomized Trial.
- 2010
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Ingår i: Transplantation. - : Williams and Wilkins. - 1534-6080 .- 0041-1337. ; 90:12, s. 1581-1589
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND.: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS.: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS.: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS.: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.
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| 5. |
- Gunst, Jesper D., et al.
(författare)
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Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
- 2021
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Ingår i: eClinicalMedicine. - : Elsevier. - 2589-5370. ; 35
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Tidskriftsartikel (refereegranskat)abstract
- Background: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials.Methods: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001,200-42.Findings: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05).Interpretation: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality.
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| 6. |
- Holmqvist, Lina, et al.
(författare)
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Exercise blood pressure and the risk of future hypertension
- 2012
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Ingår i: Journal of human hypertension. - : Springer Science and Business Media LLC. - 1476-5527 .- 0950-9240. ; 26, s. 691-695
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this prospective cohort study was to identify which blood pressure measurement during exercise is the best predictor of future hypertension. Further we aimed to create a risk chart to facilitate the evaluation of blood pressure reaction during exercise testing. A number (n=1047) of exercise tests by bicycle ergometry, performed in 1996 and 1997 were analysed. In 2007-2008, 606 patients without hypertension at the time of the exercise test were sent a questionnaire aimed to identify current hypertension. The response rate was 58% (n=352). During the 10-12 years between exercise test and questionnaire, 23% developed hypertension. The strongest predictors of future hypertension were systolic blood pressure (SBP) before exercise (odds ratios (OR) 1.63 (1.31-2.01) for 10 mm Hg difference) in combination with the increase of SBP over time during exercise testing (OR 1.12 (1.01-1.24) steeper increase for every 1 mm Hg min(-1)). A high SBP before exercise and a steep rise in SBP over time represented a higher risk of developing hypertension. A risk chart based on SBP before exercise, increase of SBP over time and body mass index was created. SBP before exercise, maximal SBP during exercise and SBP at 100 W were significant single predictors of future hypertension and the prediction by maximal SBP was improved by adjusting for time/power at which SBP max was reached during exercise testing. Recovery ratio (maximal SBP/SBP 4 min after exercise) was not predictive of future hypertension.
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| 9. |
- Nilsson, Maria, et al.
(författare)
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Self-Disorders in Asperger Syndrome Compared to Schizotypal Disorder : A Clinical Study
- 2020
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Ingår i: Schizophrenia Bulletin. - : Oxford University Press (OUP). - 1745-1701 .- 0586-7614. ; 46:1, s. 121-129
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There are historical and theoretical indications of a difference in subjective experience between autism spectrum disorder (ASD) and the schizophrenia spectrum. However, this difference has not been empirically explored. Therefore, to explore potential differences in subjective experience between the 2 spectra, we examined the presence/absence of self-disorders in Asperger syndrome/autism spectrum disorder (As/ASD) compared to schizotypal disorder (Sd). Self-disorders represent changes in basic self-awareness which have been found to accumulate within the schizophrenia spectrum. METHODS: All participants were recruited from clinical units and interviewed with a focus on the exploration of presence/absence of self-disorders, with the Examination of Anomalous Self-Experience (EASE) scale, and a general assessment of present psychopathology, with Schedules for Clinical Assessment in Neuropsychiatry (SCAN). RESULTS: A total of 51 participants (As/ASD, n = 22; Sd, n = 29) were included in the statistical analyses. When controlling for age, gender, years of education, mental problems before the age of 16, and special needs school attendance, there was a clear difference in presence/absence of self-disorders between the 2 groups, with significantly higher levels in the Sd group. Further, there was an overlap in SCAN-rated symptoms between the 2 groups. CONCLUSION: Our results indicate a significant difference between As/ASD and Sd at the level of the basic self, which, in turn, indicates that an exploration of anomalous self-experience is a valuable supplement in the clinical differentiation between As/ASD and Sd.
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| 10. |
- Nilsson, M., et al.
(författare)
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Well-Being and Self-Disorders in Schizotypal Disorder and Asperger Syndrome/Autism Spectrum Disorder
- 2020
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Ingår i: Journal of Nervous and Mental Disease. - : Ovid Technologies (Wolters Kluwer Health). - 0022-3018 .- 1539-736X. ; 208:5, s. 418-423
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Tidskriftsartikel (refereegranskat)abstract
- We explored subjective well-being in two groups of young adult participants diagnosed with either schizotypal disorder (Sd) (n = 29) or Asperger syndrome/autism spectrum disorder (As/ASD) (n = 22). Well-being was impaired in both groups and was lower in the Sd group than in the As/ASD group. Furthermore, there was a negative correlation between well-being and the presence of self-disorders. The negative effect of self-disorders on well-being was still significant when adjusted for diagnosis, age and gender, and level of function. The present findings point toward clinically important disorder-specific differences in the nature of impaired well-being between the Sd group and the As/ASD group, as there seems to be a self-disorder-driven additional contribution to impaired subjective well-being within the schizophrenia spectrum. These findings further nuance the understanding of fundamental and clinically important qualitative differences between the schizophrenia spectrum and the autism spectrum.
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