Intermittent pacing therapy favorably modulates infarct remodeling

textabstractDespite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2 h ligation of the left circumflex coronary artery followed by reperfusion. An epicardial pacing lead was implanted in the peri-infarct zone. After three days, global LV remodeling and infarct geometry were assessed using magnetic resonance imaging (MRI). Animals were stratified into MI control and IPT groups. Thirty-five days post-AMI, follow-up MRI was obtained and myofibroblast content, markers of extracellular matrix (ECM) turnover and Wnt/frizzled signaling in infarct and non-infarct control tissue were studied. Results showed that IPT had no significant effect on global LV remodeling, function or infarct mass, but modulated infarct healing. In MI control pigs, infarct mass reduction was principally due to a 26.2 ± 4.4% reduction in infarct thickness (P ≤ 0.05), whereas in IPT pigs it was mainly due to a 35.7 ± 4.5% decrease in the number of infarct segments (P ≤ 0.05), with no significant change in infarct thickness. Myofibroblast content of the infarct zone was higher in IPT (10.9 ± 2.1%) compared to MI control (5.4 ± 1.6%; P ≤ 0.05). Higher myofibroblast presence did not coincide with alterations in expression of genes involved in ECM turnover or Wnt/frizzled signaling at 5 weeks follow-up. Taken together, IPT limited infarct expansion and altered infarct composition, showing that IPT influences remodeling of the infarct zone, likely by increasing regional myofibroblast content

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage

The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH

Characteristics of the Children's Revised Impact of Event Scale in a clinically referred Dutch sample

Early identification of posttraumatic stress disorder (PTSD) in children is important to offer them appropriate and timely treatment. The Children's Revised Impact of Event Scale (CRIES) is a brief self-report measure designed to screen children for PTSD. Research regarding the diagnostic validity of the CRIES is still insufficient, has been restricted to specific populations, and sample sizes have often been small. This study evaluated the reliability and validity of the 8-item (CRIES-8) and 13-item (CRIES-13) versions of the CRIES in a large clinically referred sample. The measure was completed by 395 Dutch children (7-18 years) who had experienced a wide variety of traumatic events. PTSD was assessed using the Anxiety Disorders Interview Schedule for DSM-IV: Child and Parent version. A cutoff score of 17 on the CRIES-8 and 30 on the CRIES-13 emerged as the best balance between sensitivity and specificity, and correctly classified 78%-81% of all children. The CRIES-13 outperformed the CRIES-8, in that the overall efficiency of the CRIES-13 was slightly superior (.81 and .78, respectively). The CRIES appears to be a reliable and valid measure, which gives clinicians a brief and user-friendly instrument to identify children who may have PTSD and offer them appropriate and timely treatmen

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial

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Enhanced screening for posttraumatic stress disorder and comorbid diagnoses in children and adolescents

BACKGROUND: Posttraumatic stress disorder (PTSD) can be a debilitating disorder and often co-occurs with other psychiatric disorders, such as mood, behavioral, and anxiety disorders. Early identification of PTSD and psychiatric comorbidity is highly relevant in order to offer children appropriate and timely treatment. The Children's Revised Impact of Event Scale (CRIES-13) is a reliable and valid self-report measure designed to screen children for PTSD. However, this measure is not useful as a screen for psychiatric comorbidity in children with probable PTSD. OBJECTIVE: This study evaluated the screening accuracy of the CRIES-Plus, that is, the CRIES-13 combined with 12 additional items to detect psychiatric comorbidity. METHOD: The CRIES-Plus was completed by 398 Dutch children (7-18 years) exposed to various traumatic events. Psychiatric diagnoses were assessed using the Anxiety Disorders Interview Schedule for DSM-IV: Child version. RESULTS: Six additional items were significantly associated with mood disorders, three items were associated with behavioral disorders, and five items with anxiety disorders. Additional items associated with mood and anxiety disorders demonstrated good discriminatory ability, with cut-off scores of ≥14 and ≥10, respectively. Items associated with behavioral disorders had poor to fair discriminatory ability, with no clear cut-off point. CONCLUSIONS: Our findings support the use of the CRIES-Plus to screen for PTSD and comorbid disorders which may help clinicians in assigning appropriate follow-up diagnostic and clinical care

A parental tool to screen for posttraumatic stress in children: first psychometric results

The Children's Revised Impact of Event Scale (CRIES-13) is a brief self-report measure designed to screen children for posttraumatic stress disorder (PTSD). This study investigates the psychometric properties of a Dutch version of the CRIES-13-parent version and evaluates its correlation with the child version. A sample of 59 trauma-exposed children (8 years-18 years) and their parents completed an assessment including the CRIES-13 (child/parent version) along with the Anxiety Disorders Interview Schedule for DSM-IV: Parent version. Results demonstrated good internal consistency (α = .87) with acceptable values for the 3 subscales. A strong correlation (r = .73) with another measure of PTSD and lower correlations with a behavioral measure (r = .15 to .38) were found, confirming the convergent/divergent validity. A cutoff score ≥ 31 emerged as the best balance between sensitivity and specificity, and correctly classified 83.6% of all children as having a diagnosis of PTSD. This study provides support for the reliability and validity of the CRIES-13-parent version as a screening measure for posttraumatic stress in childre

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months. METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812. FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups. INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale. FUNDING: Fonds NutsOhra

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial

Background and ObjectivesThe ULTRA trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at 6 months. An expected proportion of the included patients experienced nonaneurysmal subarachnoid hemorrhage. In this post hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at 6 months.MethodsThe ULTRA trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013, and January 20, 2020. After confirmation of subarachnoid hemorrhage on noncontrast CT, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care or usual care only. In this post hoc analysis, we included all ULTRA participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin scale (mRS), dichotomized into good (0-3) and poor (4-6) outcomes.ResultsOf the 813 ULTRA trial patients who experienced an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio [aOR] 0.92; 95% CI 0.69-1.24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) (aOR 0.76; 95% CI 0.57-1.03), all-cause mortality at 30 days (aOR 0.91; 95% CI 0.65-1.28), and all-cause mortality at 6 months (aOR 1.10; 95% CI 0.80-1.52).DiscussionUltra-early and short-term tranexamic acid treatment did not improve clinical outcomes at 6 months in patients with aneurysmal subarachnoid hemorrhage and therefore cannot be recommended.Trial Registration InformationClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013).Classification of EvidenceThis study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage