Jessica Lo

A prospective study of the impact of serial troponin measurements on the diagnosis of myocardial infarction and hospital and six-month mortality in patients admitted to ICU with non-cardiac diagnoses

IntroductionTroponin T (cTnT) elevation is common in patients in the Intensive Care Unit (ICU) and associated with morbidity and mortality. Our aim was to determine the epidemiology of raised cTnT levels and contemporaneous electrocardiogram (ECG) changes suggesting myocardial infarction (MI) in ICU patients admitted for non-cardiac reasons.MethodscTnT and ECGs were recorded daily during week 1 and on alternate days during week 2 until discharge from ICU or death. ECGs were interpreted independently for the presence of ischaemic changes. Patients were classified into four groups: (i) definite MI (cTnT ≥15 ng/L and contemporaneous changes of MI on ECG), (ii) possible MI (cTnT ≥15 ng/L and contemporaneous ischaemic changes on ECG), (iii) troponin rise alone (cTnT ≥15 ng/L), or (iv) normal. Medical notes were screened independently by two ICU clinicians for evidence that the clinical teams had considered a cardiac event.ResultsData from 144 patients were analysed (42% female; mean age 61.9 (SD 16.9)). A total of 121 patients (84%) had at least one cTnT level ≥15 ng/L. A total of 20 patients (14%) had a definite MI, 27% had a possible MI, 43% had a cTNT rise without contemporaneous ECG changes, and 16% had no cTNT rise. ICU, hospital and 180-day mortality was significantly higher in patients with a definite or possible MI.Only 20% of definite MIs were recognised by the clinical team. There was no significant difference in mortality between recognised and non-recognised events.At the time of cTNT rise, 100 patients (70%) were septic and 58% were on vasopressors. Patients who were septic when cTNT was elevated had an ICU mortality of 28% compared to 9% in patients without sepsis. ICU mortality of patients who were on vasopressors at the time of cTnT elevation was 37% compared to 1.7% in patients not on vasopressors.ConclusionsThe majority of critically ill patients (84%) had a cTnT rise and 41% met criteria for a possible or definite MI of whom only 20% were recognised clinically. Mortality up to 180 days was higher in patients with a cTnT rise.

Respiratory morbidity at follow-up of small-for-gestational-age infants born very prematurely.

Background:The aim of this study was to determine whether small-for-gestational-age (SGA) infants born very prematurely had increased respiratory morbidity in the neonatal period and at follow-up.Methods:Data were examined from infants recruited into the United Kingdom Oscillation Study (UKOS). Of the 797 infants who were born at <29 wk of gestational age, 174 infants were SGA. Overall, 92% were exposed to antenatal corticosteroids and 97% received surfactant; follow-up data at 22–28 mo were available for 367 infants.Results:After adjustment for gestational age and sex, SGA infants had higher rates of supplementary oxygen dependency at 36 wk postmenstrual age (odds ratio (OR): 3.23; 95% confidence interval: 2.03, 5.13), pulmonary hemorrhage (OR: 3.07; 95% CI: 1.82, 5.18), death (OR: 3.32; 95% CI: 2.13, 5.17), and postnatal corticosteroid requirement (OR: 2.09; 95% CI: 1.35, 3.23). After adjustment for infant and respiratory morbidity risk factors, a lower mean birth weight z-score was associated with a higher prevalence of respiratory admissions (OR: 1.40; 95% CI: 1.03, 1.88 for 1 SD change in z-score), cough (OR: 1.28; 95% CI: 1.00, 1.65), and use of chest medicines (OR: 1.32; 95% CI: 1.01, 1.73).Conclusion:SGA infants who were born very prematurely, despite routine use of antenatal corticosteroids and postnatal surfactant, had increased respiratory morbidity at follow-up, which was not due to poor neonatal outcome.

Prediction of respiratory outcome in extremely low gestational age infants.

Background: Bronchopulmonary dysplasia (BPD) is a commonly used outcome for randomized neonatal trials. Objectives: The aim of the present study was to determine whether a diagnosis of BPD or respiratory morbidity (RM1 or RM2) at 12 months corrected age better predicted subsequent RM in extremely low gestational age infants (23-28 weeks of gestation). Methods: Initial analysis was undertaken in a development cohort of 76 infants who underwent pulmonary function tests (PFTs) at 12 months corrected age. Parents completed infant respiratory diaries 2 weeks before the PFTs. Analysis was then undertaken in a validation cohort of 227 infants whose parents completed a 4-week respiratory diary when their infant was 12 months corrected age. BPD at 28 days (BPD28d) and 36 weeks post-menstrual age (BPD36w), RM1 (≥3 days and/or nights of cough, wheeze, and/or medicine use) and RM2 (≥4 days and/or nights of cough, wheeze, and/or respiratory medicine use) each week for 2 weeks at 12 months corrected age were assessed with regard to prediction of respiratory outcomes at 24 months documented by respiratory health questionnaires. Results: BPD28d and BPD36w were not significantly associated with any respiratory outcome. Areas under the receiver operating characteristic curves were significantly better for either definition of RM than BPD28d or BPD36w for all outcomes. Conclusions: RM documented by parental completed diaries at 12 months corrected age better predicted respiratory outcome at 24 months corrected age than BPD regardless of diagnostic criteria.

Cardiac Troponin Release is Associated with Biomarkers of Inflammation and Ventricular Dilatation During Critical Illness.

Introduction: Troponin release is common during critical illness. We hypothesized that there was an association between cardiac troponin T (cTnT) and biomarkers of systemic inflammation and ventricular dilatation. Methods: In an observational prospective cohort study, we enrolled consecutive adult patients admitted for noncardiac reasons to the intensive care unit (ICU) in two tertiary care centers. We measured cTnT, C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), and N-terminal pro brain natriuretic peptide (NT-proBNP) daily in the first week, and on alternate days in the second week. Using a peak cTnT cutoff ≥15 ng/L and concomitant changes on electrocardiogram, patients were categorized as “definite myocardial infarction (MI),” “possible MI,” “cTnT rise only,” or “no cTnT rise.” Within each group, associations between CRP, IL-6, PCT, NT-proBNP, and cTnT were investigated using mixed effect models. Results: One hundred seventy-two patients were included in the analysis of whom 84% had a cTnT rise ≥15 ng/L. Twenty-one patients (12%) had a definite MI, 51 (30%) had a possible MI, and 73 (42%) had a cTnT rise only. At the time of peak cTnT, 71% of patients were septic and 67% were on vasopressors. Multivariable analysis showed a significant association between cTnT and IL-6 in all patients with a cTnT rise independent of age, gender, renal function, and cardiovascular risk factors. In patients without a definite MI, cTnT levels were significantly associated with PCT and NT-proBNP values. In patients without elevated cTnT levels, there was no associated NT-proBNP rise. Conclusions: In ICU patients admitted for non-cardiac reasons, serial cTnT levels were independently associated with markers of systemic inflammation and NT-proBNP.

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm

Importance Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. Objective Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. Materials and methods The study included 412 infants born at 23–28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. Results After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). Conclusions Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.

STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease

The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD).

Longitudinal assessment of lung function in extremely prematurely born children

To assess longitudinally small airway function in children born extremely prematurely and whether there was a correlation between airway function in infancy and at 11‐14 years.

A phase III, multi-centre, double-masked randomised controlled trial of adjunctive intraocular and peri-ocular steroid (triamcinolone acetonide) versus standard treatment in eyes undergoing vitreoretinal surgery for open globe trauma (ASCOT): statistical analysis plan

BackgroundOpen globe ocular trauma complicated by intraocular scarring (proliferative vitreoretinopathy) is a relatively rare, blinding, but potentially treatable condition for which, at present, surgery is often unsatisfactory and visual results frequently poor. To date, no pharmacological adjuncts to surgery have been proven to be effective. The aim of the Adjunctive Steroid Combination in Ocular Trauma (ASCOT) randomised controlled trial is to determine whether adjunctive steroid (triamcinolone acetonide), given at the time of surgery, can improve the outcome of vitreoretinal surgery in patients with open globe ocular trauma. This article presents the statistical analysis plan for the main publication as approved and signed off by the Trial Steering Committee prior to the first data extraction for the Data Monitoring Committee meeting report.Methods/designASCOT is a pragmatic, multi-centre, parallel-group, double-masked randomised controlled trial. The aim of the study is to recruit from 20–25 centres in the United Kingdom and randomise 300 eyes (from 300 patients) into two treatment arms. Both groups will receive standard surgical treatment and care; the intervention arm will additionally receive a pre-operative steroid combination (triamcinolone acetonide) into the vitreous cavity consisting of 4 mg/0.1 ml and 40 mg/1 ml sub-Tenon’s. Participants will be followed for 6 months post-surgery. The primary outcome is the proportion of patients achieving a clinically meaning improvement in visual acuity in the study eye at 6 months after initial surgery, defined as a 10 letter score improvement in the ETDRS (the standard scale to test visual acuity).Trial registrationISRCTN30012492. Registered on 5 September 2014.EudraCT2014-002193-37. Registered on 5 September 2014.

Making core outcomes more clinically meaningful: 2-for-the-price-of-1 with a distributional approach

Background In RCTs with a continuous outcome, it is easier to interpret a difference in proportions at high risk than the difference in means. For example when comparing lung function in two groups, a difference in proportion <10 centile may be more clinically meaningful than the difference in means. However choosing a dichotomised continuous outcome at the outset requires a larger sample than using the raw data and may also distort the true difference since data are discarded on dichotomisation.

THE RELATIONSHIP OF HYPERTENSION, DIABETES AND OTHER VASCULAR RISK FACTORS WITH POSTSTROKE COGNITIVE FUNCTION: THE STROKOG (STROKE AND COGNITION) CONSORTIUM

Background:Cognitively normal (CN) subjects with subjective cognitive decline (SCD) and emerging amyloid pathology are at increased risk of Alzheimer’s disease (AD). The ability to maintain cognition in the face of beginning neurodegeneration (ie. cognitive reserve)may be critical for the clinical progression in subjects at increased risk of AD. The aim herewas to test functional network characteristics that confer higher reserve across the early clinical spectrum of AD. Specifically, based on our previous findings in prodromal AD showing that global functional connectivity of a left frontal cortex hub (gLFC-connectivity) was associated with higher reserve (Franzmeier, Neurology, in press) we hypothesized that: 1) higher education, a protective factor, is associated with higher gLFC-connectivity 2) higher gLFC-connectivity attenuates detrimental effects of tau pathology on memory performance in preclinical and clinical stages of AD. Methods: We included 75 Ab+ individuals in different AD stages (25 CN, 23 SCD, 14 Mild Cognitive Impairment (MCI), 13 AD Dementia), as well as 50 Abindividuals (24 CN, 17 SCD, 9 MCI) all recruited within the German DELCODE study on biomarker changes in AD. GLFC-connectivity was computed as the average resting-state fMRI-connectivity between an 8mm spherical LFC-ROI (BA6/44) and each grey matter voxel. Using linear regression stratified by Ab-status, we tested whether education predicted higher gLFC-connectivity. Next, we tested whether gLFC-connectivity moderates the association between CSF-tau and the Wechsler Logical Memory delayed recall score. All regression models were controlled for age, gender and diagnosis. Results: Greater education predicted higher gLFC-connectivity inAb+ (p1⁄40.031; Figure 1) but not Ab-. The interaction gLFC-connectivity x CSF-tau was significant (p1⁄40.027) in Ab+, such that at higher gLFC-connectivity the association between higher CSF-tau and memory impairment was attenuated (Figure 2). When tested separately in preclinical (CN-Ab+ & SCD-Ab+) and clinical (MCI-Ab+ & AD dementia) groups, the interaction remained at trend level significance (preclinical: p1⁄40.067; clinical: p1⁄40.059), suggesting compensatory effects of gLFC-connectivity on Tau pathology already in preclinical AD. No interaction was found in Abparticipants. Conclusions:Higher connectivity gLFC-connectivity is a neural substrate of CR that allows compensating detrimental effects of tau pathology on memory already in CN and SCD participants.