| 2. |
- Nilsson, O. G., et al.
(författare)
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Increased Levels of Glutamate in Patients with Subarachnoid Haemorrhage as Measured by Intracerebral Microdialysis
- 1996
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Ingår i: Clinical Aspects of Microdialysis. - Vienna : Springer Vienna. - 0065-1419. - 9783709174265 - 9783709168943 ; , s. 45-47
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral ischemia associated with subarachnoid haemorrhage (SAH) may have severe consequences for neuronal function leading to reversible or permanent neurological deficits. The excitatory amino acid neurotransmitters, such as glutamate, have been shown to be of particular importance for ischemic neuronal damage. In seven patients who underwent early surgery for a ruptured intracranial aneurysm, microdialysis of glutamate was performed in order to monitor local metabolic changes in the medial temporal (all patients) and subfrontal cortex (four patients). The preliminary results indicate that: (i) extracellular glutamate concentrations may rise to very high levels after SAH and aneurysm surgery, (ii) the increased levels of excitatory amino acids correlate with the clinical course, and (iii) a rise in extracellular glutamate in one region is not necessarily paralleled with a rise in the other, as seen by the simultaneous sampling from two different vascular territories.
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| 3. |
- Singh, Jagmeet P., et al.
(författare)
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Phased target trial design and meta-analysis in a head-to-head treatment comparison
- 2023
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Ingår i: Pharmacoepidemiology and Drug Safety. - : John Wiley & Sons. - 1053-8569 .- 1099-1557. ; 32:Suppl. 1, s. 444-444
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: For conditions with rare clinical outcomes, real-world treatment comparisons are challenging to design and prone to confounding.Objectives: To present a robust methodologic approach for rigorous and transparent assessment of rare outcomes using real-world data.Methods: We emulated a target trial using an active comparator, new-user design to compare dronedarone to sotalol for rhythm control in atrial fibrillation (AF) as both are recommended for similar patient phenotypes. Using one protocol, a pre-specified stepwise approach was implemented across 4 datasets (Optum CDM; IBM MarketScan; Veterans Affairs Electronic Health Records; Swedish National Patient Register). Meta-analysis was used to ensure sufficient capture of specific, rare primary outcomes (cardiovascular (CV) hospitalization and ventricular proarrhythmia) and to evaluate consistency of findings across patient populations. Steps 1–3 focused on cohort selection, propensity score matching (PSM), baseline equipoise and residual confounding assessment via negative control outcome analyses. In steps 4–6, outcomes in the individual cohorts were analyzed using an as-treated approach and Cox proportional hazards models. Step 7 included a heterogeneity assessment, meta-analysis using fixed effects models, and hypothesis testing using a hierarchical approach. In step 8, sensitivity analyses, including E-values and Inverse Probability of Censoring Weighting, were conducted to verify the robustness of findings.Results: In step 1, 35,467 sotalol and 27,955 dronedarone patients with AF who were antiarrhythmic drug-naive were identified across databases. In steps 2–3, 23,275 dronedarone patients were PS-matched to 23,275 sotalol patients. Baseline covariates were well-balanced and little-to-no residual confounding was observed via the negative control analyses. Individual HRs were estimated in steps 4–6, and, when no significant heterogeneity between databases was observed, hazard ratios (HRs) were pooled across datasets in step 7. For example, for CV hospitalization, dronedarone was superior to sotalol with no heterogeneity (HR: 0.91; 95% CI: 0.85, 0.97; Cochran Q p-value: 0.32). Eleven sensitivity analyses were conducted in step 8 and confirmed that findings were generally robust.Conclusions: An active comparator, new-user design using the target trial approach coupled with meta-analysis generated consistent findings across databases and countries using one protocol. Similar methods, including a pre-specified stepwise approach, negative control outcome, and tests for robustness should be considered for real-world studies where specific, rare outcomes need to be examined in a rigorous and transparent way.
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