Shafagh Fallah

Minimum Oxytocin Dose Requirement After Cesarean Delivery for Labor Arrest

OBJECTIVE: To estimate the minimum effective intravenous dose of oxytocin required for adequate uterine contraction after cesarean delivery for labor arrest. METHODS: A randomized single-blinded study was undertaken in 30 parturients undergoing cesarean deliveries under epidural anesthesia for labor arrest despite intravenous oxytocin augmentation. Oxytocin was administered as a slow intravenous bolus immediately after delivery of the infant, according to a biased coin up-down sequential allocation scheme. After assisted spontaneous delivery of the placenta, the obstetrician, blinded to the oxytocin dose, assessed uterine contraction as either satisfactory or unsatisfactory. Additional boluses of oxytocin were administered as required, followed by a maintenance infusion. Data were interpreted and analyzed by a logistic regression model at 95% confidence intervals. RESULTS: All patients received oxytocin infusions at a mean ± standard deviation of 9.8 ± 6.3 hours before cesarean delivery (maximum infusion dose 10.3 ± 8.2 mU/min). The minimum effective dose of oxytocin required to produce adequate uterine response in 90% of women (ED90) was estimated to be 2.99 IU (95% confidence interval 2.32–3.67). The estimated blood loss was 1,178 ± 716 mL. CONCLUSION: Women requiring cesarean delivery for labor arrest after oxytocin augmentation require approximately 3 IU rapid intravenous infusion of oxytocin to achieve effective uterine contraction after delivery. This dose is 9 times more than previously reported after elective cesarean delivery in nonlaboring women at term, suggesting oxytocin receptor desensitization from exogenous oxytocin administration during labor. Therefore, alternative uterotonic agents, rather than additional oxytocin, may achieve superior uterine contraction and control of blood loss during cesarean delivery for labor arrest. LEVEL OF EVIDENCE: I

Predictive Value of Clinical and EEG Features in the Diagnosis of Stroke and Hypoxic Ischemic Encephalopathy in Neonates With Seizures

Background and Purpose— In neonates, the differentiation of stroke and hypoxic ischemic encephalopathy (HIE) is important. Neuroimaging presents technical challenges in unstable neonates, resulting in frequently delayed or missed diagnosis of stroke. Differentiating clinical and electroencephalographic (EEG) features would assist physicians in the timely diagnosis. We sought to determine, in neonates with seizures, clinical and EEG features that differentiate stroke and HIE. Methods— Retrospective cohort study comparing clinical, seizure, and EEG features in term neonates with ischemic stroke or HIE and seizures within 7 days after birth, admitted at The Hospital for Sick Children. Putative clinical and EEG predictors of stroke were analyzed with univariate and multivariate methods. Results— Sixty-two newborns with stroke (n=27) or HIE (n=35) were studied. With univariate analysis, predictors of stroke included delayed seizure onset (≥12-hours after birth) (P<0.0001; OR, 26.4; 95% CI, 6.8, 102.5), focal motor seizures (P=0.001; OR, 7.2; 95% CI, 2.0, 26.0) and pattern of neurological abnormalities (P<0.0001). With multivariate analysis, delayed seizure onset (P<0.0001; OR 39.7; 95% CI, 7.3, 217.0) and focal motor seizures (P=0.007; OR, 13.4; 95% CI, 2.1, 87.9) predicted stroke. Presence of both predictors had 100% positive predictive value and specificity, 61% negative predictive value and 37% sensitivity. Conclusions— In neonates, onset of seizures beyond 12 hours of birth and clinically observed focal seizures are predictive of stroke. These preinvestigation indicators of stroke may facilitate earlier diagnosis and institution of specific management strategies.

Usefulness of Improvement in Walking Distance Versus Peak Oxygen Uptake in Predicting Prognosis After Myocardial Infarction and/or Coronary Artery Bypass Grafting in Men

Information is limited on the influence of a change in fitness and/or physical activity on mortality in cardiac patients who undergo exercise rehabilitation. This was studied in 6,956 men (4,713 with myocardial infarctions, 2,243 who underwent coronary bypass surgery) completing a 12-month walking-based training regimen and followed for a median of 9 years (range 4 to 26; 67,820 patient-years). Peak oxygen uptake (VO2peak) was measured at the beginning and the end of the program, and walking distance and pace were recorded weekly. These and other pertinent data were entered into a Cox proportional-hazards model and tested for associations with time to cardiac and all-cause death. In total, 2,016 deaths were recorded (737 cardiac, 1,279 all-cause). The mean increase in VO2peak was 4.9 ml/kg/min (95% confidence interval [CI] 4.7 to 5.0, p <0.0001), and the mean increase in distance walked was 2.1 mi (95% CI 2.0 to 2.1, p <0.0001). Increase in VO2peak was significant on univariate analysis (hazard ratio [HR] 0.98) but not on multivariate analysis. Distance increase was a significant predictor of cardiac and all-cause death on multivariate analysis, with each 1-mi improvement conferring a 20% reduction in cardiac death (HR 0.80, 95% CI 0.71 to 0.87, p <0.0001). When categorized into groups of <1.3 (referent), 1.3 to 2.8, and >2.8 mi, increased walking distance of 1.3 to 2.8 and of >2.8 mi yielded 24% (HR 0.76, 95% CI 0.62 to 0.92, p = 0.005) and 48% (HR 0.52, 95% CI 0.40 to 0.68, p <0.0001) reductions in cardiac death, respectively. In conclusion, in men who underwent an exercise rehabilitation program, improvement in walking distance was a strong independent predictor, and a greater guide to prognosis, than gains in VO2peak.

Complications of exteriorized compared with in situ uterine repair at cesarean delivery under spinal anesthesia: a randomized controlled trial.

OBJECTIVE: To compare intraoperative complications of exteriorized and in situ uterine repair during elective cesarean delivery under spinal anesthesia. METHODS: This study was a randomized, single-blinded trial in 80 women undergoing elective cesarean delivery under spinal anesthesia. Patients were randomly assigned to exteriorized or in situ uterine repair. Obstetricians were asked to perform assisted delivery of the placenta. Spinal anesthesia and oxytocin management were standardized. Phenylephrine was used to maintain systolic blood pressure within 10% of the baseline. The primary outcome was intraoperative, postdelivery nausea or vomiting. RESULTS: Postdelivery nausea or vomiting (18% compared with 38%; P=.04) and tachycardia (3% compared with 18%; P=.03) were significantly reduced in the in situ group compared with the exteriorized group. The duration of uterine repair was significantly shorter in the exteriorized group (median 10 minutes [first and third quartiles 9, 13], compared with 11 minutes [9, 15]) (P=.04). The duration of surgery (36 minutes [30, 41] compared with 37 minutes [30, 45]) and estimated blood loss (mean±standard deviation 625±489 mL compared with 653±416 mL) were similar between the in situ and the exteriorized groups. There was no correlation between duration of uterine repair and estimated blood loss. CONCLUSION: Exteriorization of the uterus for repair is associated with an increased incidence of nausea and vomiting and tachycardia during cesarean delivery under spinal anesthesia. Uterine repair should be done in situ where possible. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00452972 LEVEL OF EVIDENCE: I

Agreement of Carbon Dioxide Levels Measured by Arterial, Transcutaneous and End Tidal Methods in Preterm Infants ≤28 Weeks Gestation

OBJECTIVE:To assess the agreement of transcutaneous carbon dioxide (TcPCO2) and end tidal carbon dioxide (PetCO2) with arterial carbon dioxide (PaCO2) values in infants < 28 weeks gestational age.STUDY DESIGN:In all, 27 ventilated preterm infants were prospectively studied. PaCO2 was compared with TcPCO2 and PetCO2 measured at three similar time points within first 24 hours after birth.RESULTS:The Intraclass correlation coefficients for TcPCO2 and PaCO2 were 0.45, 0.73 and 0.53; and for PetCO2 and PaCO2 were 0.61, 0.56 and 0.57 at 4, 12 and 24 hours after birth, respectively.CONCLUSION:A moderate agreement with a wide variation in individual values was observed between noninvasive methods and PaCO2 in preterm infants in the first 24 hours. Noninvasive monitoring methods cannot be substituted for PaCO2 analyses in preterm infants during this critical period.

Estimating Number of Clusters Based on a General Similarity Matrix with Application to Microarray Data

Many clustering methods require that the number of clusters believed present in a given data set be specified a priori, and a number of methods for estimating the number of clusters have been developed. However, the selection of the number of clusters is well recognized as a difficult and open problem and there is a need for methods which can shed light on specific aspects of the data. This paper adopts a model for clustering based on a specific structure for a similarity matrix. Publicly available gene expression data sets are analyzed to illustrate the method and the performance of our method is assessed by simulation.

Genome-wide linkage analysis of systolic blood pressure slope using the Genetic Analysis Workshop 13 data sets

Systolic blood pressure (SBP) is an age-dependent complex trait for which both environmental and genetic factors may play a role in explaining variability among individuals. We performed a genome-wide scan of the rate of change in SBP over time on the Framingham Heart Study data and one randomly selected replicate of the simulated data from the Genetic Analysis Workshop 13. We used a variance-component model to carry out linkage analysis and a Markov chain Monte Carlo-based multiple imputation approach to recover missing information. Furthermore, we adopted two selection strategies along with the multiple imputation to deal with subjects taking antihypertensive treatment. The simulated data were used to compare these two strategies, to explore the effectiveness of the multiple imputation in recovering varying degrees of missing information, and its impact on linkage analysis results. For the Framingham data, the marker with the highest LOD score for SBP slope was found on chromosome 7. Interestingly, we found that SBP slopes were not heritable in males but were for females; the marker with the highest LOD score was found on chromosome 18. Using the simulated data, we found that handling treated subjects using the multiple imputation improved the linkage results. We conclude that multiple imputation is a promising approach in recovering missing information in longitudinal genetic studies and hence in improving subsequent linkage analyses.

Modeling complex disease with demographic and environmental covariates and a candidate gene marker.

We randomly chose replicates 28 and 29 of the simulated data sets of Genetic Analysis Workshop 12 to model the dependence of affection status on covariates, quantitative traits, and genes using all living pedigree members. First we explored the relationship of affection status to demographic and environmental factors using logistic regression and the Cox proportional hazards models. In the second stage of our analyses the generalized transmission disequilibrium test (GTDT) was applied to nuclear families with at least two affected siblings to select single markers and high‐risk alleles, which were tested in the population association analyses including all pedigree members. Multiple logistic regression models were fitted to investigate the joint contributions of genetic and nongenetic factors and a block‐recursive modeling approach was adopted to study inherent hierarchical dependence structure in the data. We found that allele 2 on marker 35 of chromosome 6 is associated with higher risk compared with the other 3 alleles of this marker. In addition to this significant genetic effect, age at exam and four of the five quantitative traits (QT1, QT2, QT4, and QT5) had a significant association with the disease. Our results were obtained without knowledge of the true disease generating models.