Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations.

INTRODUCTION: Oral corticosteroids are the cornerstone of acute asthma management in the emergency department. Recent evidence has raised doubts about the efficacy of this treatment in preschool-aged children with viral-induced wheezing and in smoking adults. The aims of the study were to: (1) document the magnitude of response to oral corticosteroids in children presenting to the emergency department with moderate or severe asthma; (2) quantify potential determinants of response to corticosteroids and (3) explore the role of gene polymorphisms associated with the responsiveness to corticosteroids. METHODS AND ANALYSIS: The design is a prospective cohort study of 1008 children aged 1-17 years meeting a strict definition of asthma and presenting with a clinical score of ≥4 on the validated Pediatric Respiratory Assessment Measure. All children will receive standardised severity-specific treatment with prednisone/prednisolone and cointerventions (salbutamol with/without ipratropium bromide). Determinants, namely viral aetiology, environmental tobacco smoke and single nucleotide polymorphism, will be objectively documented. The primary efficacy endpoint is the failure of emergency department (ED) management within 72 h of the ED visit. Secondary endpoints include other measures of asthma severity and time to recovery within 7 days of the index visit. The study has 80% power for detecting a risk difference of 7.5% associated with each determinant from a baseline risk of 21%, at an α of 0.05. ETHICS AND DISSEMINATION: Ethical approval has been obtained from all participating institutions. An impaired response to systemic steroids in certain subgroups will challenge the current standard of practice and call for the immediate search for better approaches. A potential host-environment interaction will broaden our understanding of corticosteroid responsiveness in children. Documentation of similar effectiveness of corticosteroids across determinants will provide the needed reassurance regarding current treatment recommendations. RESULTS: Results will be disseminated at international conferences and manuscripts targeted at emergency physicians, paediatricians, geneticists and respirologists. TRIAL REGISTRATION NUMBER: This study is registered at Clinicaltrials.gov (NCT02013076).

Maternal factors implicated in fetal bradycardia after combined spinal epidural for labour pain.

BACKGROUND AND OBJECTIVE: Combined spinal epidural analgesia is effective for fast relief of severe labour pain but has been associated with worrisome decreases in fetal heart rate. Since the reasons for this phenomenon remain elusive, some anaesthesiologists may abstain from using this technique. We postulated that factors unrelated to the neuraxial technique could play a role in the decrease in fetal heart rate. To our knowledge, no prospective study has previously looked into this possibility. METHODS: We collected prospective data on 223 consecutive patients who received combined spinal epidural analgesia (123) or epidural analgesia (100). Maternal blood pressure, analogue pain scores, exogenous infusion of oxytocin, cervical dilatation, maternal age, parity and ethnicity were collected and correlated with the occurrence of decreases in fetal heart rate post combined spinal epidural. RESULTS: Univariate analysis showed a correlation between the incidence of fetal bradycardia and higher maternal pain scores, older maternal age, and combined spinal epidural analgesia. Multivariate analysis revealed that only pain scores and maternal age were independent predictors of fetal bradycardia post neuraxial blockade. CONCLUSIONS: Maternal pain scores and older maternal age are factors unrelated to the neuraxial technique that are independent predictors of fetal bradycardia after neuraxial analgesia for labour.

Protective effect of pyridoxal-5-phosphate (MC-1) on perioperative myocardial infarction is independent of aortic cross clamp time: results from the MEND-CABG trial.

AIM: Aortic cross-clamp time remains a significant marker of mortality and morbidity after coronary artery bypass graft (CABG) surgery. Pyridoxal-5-phosphate (MC-1), blocking purinergic receptors and intracellular influx of calcium, was shown to decrease the incidence of perioperative myocardial infarction in the prospective, randomized, double-blinded MC-1 to Eliminate Necrosis and Damage in CABG (MEND-CABG) clinical trial. METHODS: We studied the relationship between treatment with MC-1 and aortic cross-clamping relative to the incidence of cardiovascular (CV) death and myocardial infarction (MI) in the trial that enrolled 901 high-risk patients undergoing CABG with cardiopulmonary bypass. Patients were randomized to receive either placebo, MC-1 250 mg/day or MC-1 750 mg/day starting 3-10 h before CABG and continued for 30 days after surgery. Serial creatine kinase-myocardial band (CK-MB) determinations, ECGs and clinical evaluations were performed. RESULTS: Cross-clamping time increased the event rate of death and MI with an odds ratio (95% confidence interval) of 1.67 (1.17-2.37, P=0.0044). Treatment with MC-1 decreased the rate of events (P=0.0073) with odds ratios of 0.52 (0.31-0.88 for MC-1 250 mg/day versus placebo) and 0.48 (0.29-0.82 for MC-1 750 mg/day versus placebo). There was no interaction between cross-clamp time and treatment (P=0.61) on the occurrence of the combined endpoint. CONCLUSION: MC-1 decreased the incidence of CV death and MI (CK-MB >or=100 ng/mL) during the first 90 days after CABG in the MEND-CABG trial. Although longer aortic clamping time increased the risk of cardiovascular events, the protective effect of MC-1 was independent of ischemic time during CABG.

Left ventricular end-diastolic pressure is a predictor of mortality in cardiac surgery independently of left ventricular ejection fraction.

BACKGROUND: Several risk factors have been shown to increase mortality in cardiac surgery. However, the importance of left ventricular end-diastolic pressure (LVEDP) as an independent risk factor before cardiac surgery is unclear. Method. This observational study investigated 3024 consecutive adult patients who underwent cardiac surgical procedures at the Montreal Heart Institute from 1996 to 2000. The primary outcome was in-hospital mortality with 99 deaths (3.3%) among these patients. RESULTS: Of the 35 variables subjected to univariate analysis, 23 demonstrated a significant association with mortality. Stepwise multivariate logistic regression identified LVEDP as an independent predictor of mortality after cardiac surgery. The area under the receiver operating characteristic curve of the model predicting mortality was 0.85. CONCLUSIONS: Elevated LVEDP is an independent predictor of mortality in cardiac surgery. This variable is independent of left ventricular ejection fraction.

Detection of renal artery stenosis: prospective comparison of captopril-enhanced Doppler sonography, captopril-enhanced scintigraphy, and MR angiography.

OBJECTIVE: The objective of our study was to compare the value of captopril-enhanced Doppler sonography, captopril-enhanced renal scintigraphy, and gadolinium-enhanced MR angiography for detecting renal artery stenosis. SUBJECTS AND METHODS: Forty-one patients with suspected renovascular hypertension were prospectively examined with captopril-enhanced Doppler sonography, captopril-enhanced renal scintigraphy, gadolinium-enhanced MR angiography, and catheter angiography. The sensitivity and specificity of each technique for detecting renal artery stenosis measuring 50% or greater and 70% or greater were compared using the McNemar test. Positive and negative predictive values were estimated for populations with 5% and 30% prevalence of renal artery stenosis. Kappa values for interobserver agreement were assessed for both gadolinium-enhanced MR angiography and catheter angiography. RESULTS: For detecting renal artery stenosis measuring 50% or greater, the sensitivity of gadolinium-enhanced MR angiography (96.6%) was greater than that of captopril-enhanced Doppler sonography (69%, p = 0.005) and captopril-enhanced renal scintigraphy (41.4%, p = 0.001). No significant difference in specificity was observed among modalities. For renal artery stenosis measuring 50% or greater, positive and negative predictive values were respectively 62% and 86% for captopril-enhanced Doppler sonography, 49% and 76% for captopril-enhanced renal scintigraphy, and 53% and 98% for gadolinium-enhanced MR angiography. Interobserver agreement was high for both gadolinium-enhanced MR angiography (kappa = 0.829) and catheter angiography (kappa = 0.729). CONCLUSION: Gadolinium-enhanced MR angiography is the most accurate noninvasive modality for detecting renal artery stenosis greater than or equal to 50%. The use of captopril-enhanced Doppler sonography in combination with gadolinium-enhanced MR angiography for identifying renal artery stenosis needs to be evaluated with a cost-effectiveness analysis.

Corneal transplant tolerance of cryopreservation.

PURPOSE: To study the outcome of corneal transplants performed with cryopreserved tissue. METHODS: Maisonneuve-Rosemont Hospital medical records of all corneal transplantations performed with cryopreserved tissue by one surgeon (M.L.F.) between March 1978 and April 1991 were reviewed. The Kaufman--Capella cryopreservation technique was used. Corneas were cryopreserved for periods of 3 days to 16.8 years (mean, 4.6 years) before transplantation. RESULTS: We report a mean follow-up of 54 months (range, 2.8--151.3 months). Survival analysis showed the probability of a clear graft to be 76% at 1 year and 73.2% at 2 years. At the time of the last visit, visual acuity was 20/40 or better in 61 eyes (49.2%). The mean postoperative pachometry was 0.58 mm (range, 0.50--0.75 mm). Specular microscopy performed in 57 eyes showed a mean endothelial cell count of 938 cells/mm(2) 55.1 months (range, 2.9--151.3 months) after surgery. For comparison purposes, the outcome of a subgroup of cryopreserved (n = 33) and noncryopreserved (n = 26) corneas transplanted by the same surgeon between April 1986 and April 1990 was studied. CONCLUSION: Despite an increase in the primary failure rate and higher initial endothelial cell loss, cryopreserved transplants are viable. Although we do not recommend cryopreservation of corneas for elective surgery, we consider that cryopreserved corneas can be very useful in emergency situations when tissue availability is a problem.

Volumetric quantification of coronary artery calcifications using dual-slice spiral CT scanner: improved reproducibility of measurements with 180 degrees linear interpolation algorithm.

PURPOSE: The purpose of this work was to determine the reproducibility of coronary total calcium score (TCS) with dual-slice helical CT and compare three acquisition protocols. METHOD: Fifty patients (59 +/- 10 years old) underwent dual-slice helical CT (collimation = 2 x 2.5 mm) and coronary angiography. Two successive scans were performed, resulting in three sets of images: pitch = 1, 360 degrees linear interpolation (LI) (A360); pitch = 1, 180 degrees LI (A180); and pitch = 1.5, 180 degrees LI (B180). TCS values, calculated using a volumetric method with a threshold of 90 HU, were compared, and the interscan variation was determined. Diagnostic performances were compared with receiver operating characteristic curves. RESULTS: Protocol A360 provided significantly lower TCS than protocols A180 and B180 (p < 0.0001). No statistical difference was seen between A180 and B180, which provided the lowest interscan variation (40 +/- 58%). However, no significant clinical impact of the observed interscan variations was found. CONCLUSION: Reproducibility of TCS with dual-slice helical CT is improved by the 180 LI algorithm. However, dual-slice helical CT is not sufficiently reproducible to allow serial quantification of TCS over time.

Hydroxyl radical production in the cortex and striatum in a rat model of focal cerebral ischemia.

BACKGROUND: Increases in hydroxyl radical production have been used as evidence of oxidative stress in cerebral ischemia/ reperfusion. Ischemia can also induce increased dopamine release from the striatum that may contribute to hydroxyl radical formation. We have compared hydroxyl radical production in the cortex and striatum as an index of oxidative stress in a rat model of focal cerebral ischemia with cortical infarction. METHODS: Using a three vessel occlusion model of focal cerebral ischemia combined with bilateral microdialysis, hydroxylation of 4-hydroxybenzoate (4HB) was continuously monitored in both hemispheres in either the lateral striatum or frontoparietal cortex. The ischemia protocol consisted of one hour equilibration, 30 min of three vessel occlusion, then release of the contralateral common carotid artery (CCA) for 2.5 h. RESULTS: Induction of ischemia resulted in a 30-fold increase in dopamine release in the lateral striatum. Compared to the nonischemic striatum, the ratio of the hydroxylation product 3,4-dihydroxybenzoate (34DHB) to 4HB (trapping agent) in the ipsilateral striatum increased significantly 30 min after ischemia induction. In contrast, during the 30 min of three vessel occlusion there was no increase in the ratio in the cortex. Following the release of the contralateral CCA, the ratio from the ischemic cortex increased significantly compared to sham-operated animals. However, under all circumstances, the 34DHB/4HB ratio was greater in the striatum than in the cortex. CONCLUSION: The increase in the 34DHB/4HB ratio in the lateral striatum coincides with the increased dopamine release suggesting a role for dopamine oxidation in the increased production of hydroxyl radicals. The significant increase in the ratio from the ischemic cortex compared to that from the sham-operated animals is consistent with increased oxidative stress induced by ischemia. However, the lower 34DHB/4HB ratio in the cortex which does not receive dopaminergic innervation compared to the striatum suggests a different mechanism for hydroxyl radical production. Such an alternate mechanism may represent a more toxic oxidative insult that contributes to infarction.

Protected specimen brush or bronchoalveolar lavage to diagnose bacterial nosocomial pneumonia in ventilated adults: a meta-analysis.

OBJECTIVE: We conducted a meta-analysis by using summary receiver operating characteristic curves to compare the diagnostic value for bacterial nosocomial pneumonia of the following: a) quantitative culture (colony-forming units per milliliter or CFU/mL) of respiratory secretions collected with a bronchoscopic protected specimen brush (PSB); b) quantitative culture of a bronchoscopic bronchoalveolar lavage (BAL); and c) the percentage of infected cells (IC) in BAL. DATA SOURCES: All studies published in the English or the French language, through January 1, 1995, on the evaluation of PSB or BAL for the diagnosis of pneumonia were considered for analysis. The relevant literature was identified through computer and reference searching and by experts in the field. STUDY SELECTION: A study was included if at least two of three independent readers regarded its purpose as the evaluation of CFU-PSB, CFU-BAL, or IC-BAL for the diagnosis in human beings of bacterial nosocomial pneumonia in ventilated adults and if the study was prospective and published in a peer-reviewed journal. DATA EXTRACTION: Three readers reviewed all published articles and decided whether to include each study; consensus was defined as agreement by at least two readers. The authors of each original article included in the meta-analysis were asked to complete a questionnaire in which they were asked to check and to correct the data extracted by one of the independent readers. DATA SYNTHESIS: Summary receiver operating characteristic curves were used to compare the efficacy of three diagnostic tests. Eighteen studies on CFU-PSB (795 patients) were included, as well as 11 studies on CFU-BAL (435 patients) and 11 on IC-BAL (766 patients). The accuracy of these tests was not different. However, it seems that administration of previous antibiotics markedly decreased accuracy of CFU-PSB (p = .0002) but not the accuracy of CFU-BAL and that of IC-BAL. CONCLUSION: Both PSB and BAL are reliable to diagnose bacterial nosocomial pneumonia. Because CFU-BAL and IC-BAL seemed more resistant to the effects of antibiotics, we recommend BAL rather than PSB if the patient is already receiving antibiotics.

Study of psychosocial parameters related to the survival rate of renal transplantation in children.

The purpose of the present study was to assess the effect of intelligence, schooling, psychomotor, emotional, and social status on renal graft survival in children. Sixty-two cadaver renal transplant recipients were evaluated retrospectively and the influence of sex, age, weight, and the use of cyclosporin A (CyA) on the success rate of the graft from 1 to 5 years later was analyzed. Psychological and social scores were devised and included as factors predictive of survival of the graft. Univariate analysis showed that the following variables predicted renal graft survival: the use of CyA (P = 0.0002), pre-transplant dialysis (P = 0.04), weight at the time of transplantation (P = 0.072), and psychological scores (P = 0.064). Association analysis demonstrated that pre-transplantation dialysis was only a chance association and therefore the parameter was discarded. Multivariate analysis showed that the predictive parameters were the use of CyA, sex, weight in kilograms, and the psychological score. An equation was then derived from variables that predict the probability that a specific patient's graft will survive more than t months. This equation is the estimated survival distribution function and is as follow: S (t) = Exp {-Exp[-(0.8882x1 - 1.827x2 + 0.037x3 - 0.1746x4) + ln t - 4.7862]} where S (t) = the survival at t months post transplantation, x1 = sex (male 1, female 2), x2 = CyA (yes 1, no 2), x3 = weight in kilograms, and x4 = psychological score. The major impact of psychological factors on renal graft survival was surprising.

Should we patch corneal erosions?

OBJECTIVE: To study the effect of patching on the speed of reepithelialization, slit-lamp signs of epithelial wound healing, and patient discomfort following a corneal abrasion. METHODS: Forty-eight eyes of 46 patients with corneal erosion sparing Bowman membrane were randomized into 2 groups: with or without patching. Slit-lamp examination and photographs of the fluorescein-stained cornea were performed on a daily basis until reepithelialization was complete. Photographs were analyzed using computer-assisted planimetry. RESULTS: No statistically significant difference was found between patched (n = 25) and nonpatched (n = 22) eyes for the mean size of the initial erosion (patched eyes, 23.7 mm2; nonpatched eyes, 18.9 mm2; P = .42), linear speed of reepithelialization (reduction over time of the radius of the largest circle included in the erosion: patched eyes, 0.0375 mm/h; nonpatched eyes, 0.0353 mm/h; P = .78), and surface speed of reepithelialization (reduction over time of the erosion area: patched eyes, 0.6510 mm2/h; nonpatched eyes, 0.5657 mm2/h; P = .60). The power to detect a 12-hour delay of epithelial closure was 95%. There were no significant differences between the 2 groups for pain, analgesia, insomnia, aspect of the epithelial border, intensity and duration of stromal edema, Descemet folds, anterior uveitis, and filaments. CONCLUSIONS: Patching a corneal erosion does not significantly accelerate reepithelialization and does not alter the epithelial wound healing pattern. It does not reduce the incidence and severity of inflammation nor relieve pain when compared with treatment without patching.

Anterior stromal punctures for bullous keratopathy.

OBJECTIVE: To evaluate the therapeutic effects of anterior stromal punctures (ASP) in patients with bullous keratopathy (BK). PATIENTS AND METHODS: Twenty-seven patients awaiting penetrating keratoplasty with a diagnosis of BK were examined. They were seen before treatment with ASP and 1, 4, and 12 weeks after treatment. The examination included slit-lamp examination, photography of the cornea, ultrasonic pachymetry, central esthesiometry, and pneumotonometry. Subjective evaluations of pain, discomfort, and photophobia were also done using a visual scale model. Photographs were analyzed by computer-assisted planimetry and used to measure the corneal surface covered by bullae and microcysts. Pretreatment and posttreatment values (mean +/- SEM) were compared using the Student paired t test. RESULTS: At 3 months, a significant reduction in pain was noted. A decrease in the mean corneal surface covered by bullae (BKPreASP = 2733 +/- 553 microns2; BK3mo = 1006 +/- 356 microns2, P = .004) was observed. A decrease in the esthesiometry (E) measurement (EPreASP = 3.5 +/- 0.4 cm; E3mo = 1.3 +/- 0.3 cm, P < .001), an increase in corneal thickness ([CT] CTPreASP = 869 +/- 24 microns; CT3mo = 902 +/- 21 microns, P < .001), and a decrease in the number of quadrants through which iris (I) details could be seen (IPreASP = 1.7 +/- 0.3; I3mo = 1.2 +/- 0.3, P = .015) were also noted. These findings corroborate the clinical observation of increased subepithelial fibrosis following ASP. CONCLUSIONS: Anterior stromal punctures reduce bullae formation and alleviate pain in patients with BK, and they constitute a valuable alternative to penetrating keratoplasty should surgery be delayed or contraindicated.

Reference values obtained by kernel-based estimation of quantile regressions.

In this paper, we study the problem of estimating non-parametrically a quantile regression curve as it applies to computing reference values. We propose an automatic procedure that uses a symmetrized nearest-neighbor kernel estimator of conditional distributions. We also discuss ways of measuring the dispersion of quantile regression estimator. One is based on the asymptotic distribution of such quantiles, while the other relies on the bootstrap method. The results of a small simulation study show that the methods of the paper perform rather well even in a situation where a good parametric solution is available. As an example, we analyze a small part of a data set that was collected to establish reference values for blood velocity in different parts of the umbilical cord of human fetuse as they grow toward birth.

Predicting blood loss in surgery for idiopathic scoliosis.

The authors attempted to determine the relative importance of factors that influence bleeding during and after spinal fusion. Data from 30 ASA I patients with idiopathic scoliosis were prospectively collected and analyzed. Intraoperative bleeding was 1971 +/- 831 ml (mean +/- SD) (61.5 +/- 27% of estimated blood volume (EBV) and correlated with the number of fused vertebrae (r = 0.66, P < 0.0001) and the duration of surgery (r = 0.46, P = 0.0105). There was no correlation between intraoperative bleeding and the Cobb curve angle (43 to 86 degrees), the mean arterial blood pressure (MAP) (63 to 86 mmHg), the central venous pressure (CVP), the quantity of epinephrine infiltrated, muscle relaxants or opioids used, nor in the type of opioids used, the minimal body temperature or whether stored or autologous blood was used. Postoperative bleeding was 1383 +/- 369 ml (43.1 +/- 11.7% of EBV) and correlated with the length of time the Hemovac drain was in place (r = 0.40, P = 0.0285) and MAP (r = 0.40, P = 0.0285). There was no correlation between postoperative and intraoperative bleeding nor in the number of fused vertebrae. Six patients had greater postoperative than intraoperative bleeding. The total bleeding (intra- plus postoperative) was 3347 +/- 920 ml (104.2 +/- 30.6 of EBV) and correlated with the number of fused vertebrae (r = 0.63, P = 0.0001) and with the duration of surgery (r = 0.42, P = 0.0208). We conclude that the number of fused vertebrae is the key factor in predicting intraoperative and total bleeding. Postoperative bleeding is considerable (up to 76.9% of EBV).(ABSTRACT TRUNCATED AT 250 WORDS)

Reference values for Doppler velocimetric indices from the fetal and placental ends of the umbilical artery during normal pregnancy.

A range-gated Doppler ultrasound system combined with a real-time imaging system was used to determine arterial blood velocity values from the fetal and placental ends of the umbilical cord in 269 normal pregnancies between 17 and 40 weeks, menstrual age. The systolic-diastolic ratio (S/D), pulsatility index (PI), and resistance index (RI) were higher at the fetal end compared to the placental end of the cord. The individual differences in these Doppler indices, obtained between the fetal and placental recording sites, were inversely related to menstrual age: S/D: r = -0.38, p < 0.001; PI: r = -0.25, p < 0.001; and RI: r = -0.15, p < 0.01. After normalization for the angle of insonation, the peak systolic velocity was higher and the end-diastolic velocity was lower at the fetal than at the placental end of the cord. It is concluded that routine recordings for Doppler velocimetric indices should take into account the recording site on the umbilical cord in order to reduce methodological sources of variance, especially during midgestation. Furthermore, the data presented here in the form of the median and percentile values are proposed as normal reference values to facilitate this procedure.