Predicting risk of peripartum blood transfusion during vaginal and cesarean delivery: A risk prediction model.

OBJECTIVE: The objective of this study is to develop a model that will help predict the risk of blood transfusion using information available prior to delivery. STUDY DESIGN: The study is a secondary analysis of the Consortium on Safe Labor registry. Women who had a delivery from 2002 to 2008 were included. Pre-delivery variables that had significant associations with transfusion were included in a multivariable logistic regression model predicting transfusion. The prediction model was internally validated using randomly selected samples from the same population of women. RESULTS: Of 156,572 deliveries, 5,463 deliveries (3.5%) required transfusion. Women who had deliveries requiring transfusion were more likely to have a number of comorbidities such as preeclampsia (6.3% versus 4.1%, OR 1.21, 95% CI 1.08-1.36), placenta previa (1.8% versus 0.4%, OR 4.11, 95% CI 3.25-5.21) and anemia (10.6% versus 5.4%, OR 1.30, 95% CI 1.21-1.41). Transfusion was least likely to occur in university teaching hospitals compared to community hospitals. The c statistic was 0.71 (95% CI 0.70-0.72) in the derivation sample. The most salient predictors of transfusion included type of hospital, placenta previa, multiple gestations, diabetes mellitus, anemia, asthma, previous births, preeclampsia, type of insurance, age, gestational age, and vertex presentation. The model was well-calibrated and showed strong internal validation. CONCLUSION: The model identified independent risk factors that can help predict the risk of transfusion prior to delivery. If externally validated in another dataset, this model can assist health care professionals counsel patients and prepare facilities/resources to reduce maternal morbidity.

Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial.

BACKGROUND: The appropriate dose of intrathecal morphine for post-cesarean analgesia is unclear. With the inclusion of routine non-steroidal anti-inflammatory drugs, the required dose of morphine may be significantly less than the 200-300µg common a decade ago. We performed a two-center, prospective, randomized, blinded trial comparing three doses of intrathecal morphine, combined with routine intravenous ketorolac, in 144 healthy women undergoing elective cesarean delivery. METHODS: Patients received an intrathecal injection of hyperbaric bupivacaine 12mg, fentanyl 15µg and a randomized dose of 50, 100, or 150µg morphine in a volume of 2.2mL. Patients received intravenous ketorolac 30mg before leaving the operating room and 15mg intravenously every 6h for the duration of the study (24h). All received postoperative patient-controlled intravenous morphine. The primary endpoint was total intravenous morphine administered postoperatively over 24h, analyzed using mixed model regression. RESULTS: There were no differences between dose groups (or institutions) in intravenous morphine use over 24h. Visual analog scale scores for pain and nausea did not differ. Pruritus was greater in the 100 and 150µg groups than the 50µg group at 6h and 12h, but there was no difference between groups in nausea or pruritus treatments. Respiratory depression or significant sedation did not occur. CONCLUSION: The dose-response relationship of intrathecal morphine for multimodal post-cesarean analgesia suggests that 50µg produces analgesia similar to that produced by either 100µg or 150µg.

Genetic testing in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cost-effectiveness analysis.

BACKGROUND: The CYP2C19 genotype is a predictor of adverse cardiovascular events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) treated with clopidogrel. OBJECTIVES: We aimed to evaluate the cost-effectiveness of a CYP2C19*2 genotype-guided strategy of antiplatelet therapy in ACS patients undergoing PCI, compared with two 'no testing' strategies (empiric clopidogrel or prasugrel). METHODS: We developed a Markov model to compare three strategies. The model captured adverse cardiovascular events and antiplatelet-related complications. Costs were expressed in 2010 US dollars and estimated using diagnosis-related group codes and Medicare reimbursement rates. The net wholesale price for prasugrel was estimated as $5.45 per day. A generic estimate for clopidogrel of $1.00 per day was used and genetic testing was assumed to cost $500. RESULTS: Base case analyses demonstrated little difference between treatment strategies. The genetic testing-guided strategy yielded the most QALYs and was the least costly. Over 15 months, total costs were $18 lower with a gain of 0.004 QALY in the genotype-guided strategy compared with empiric clopidogrel, and $899 lower with a gain of 0.0005 QALY compared with empiric prasugrel. The strongest predictor of the preferred strategy was the relative risk of thrombotic events in carriers compared with wild-type individuals treated with clopidogrel. Above a 47% increased risk, a genotype-guided strategy was the dominant strategy. Above a clopidogrel cost of $3.96 per day, genetic testing was no longer dominant but remained cost-effective. CONCLUSIONS: Among ACS patients undergoing PCI, a genotype-guided strategy yields similar outcomes to empiric approaches to treatment, but is marginally less costly and more effective.

Centrifugation speed affects light transmission aggregometry.

BACKGROUND: Light transmission aggregometry (LTA) is considered the gold standard for investigating platelet activity ex vivo. However, LTA protocols are not standardized, and differences in LTA procedure are a potential source of variance in results. Centrifugation speed is an essential component of platelet preparation in LTA, has yet to be standardized, and may affect platelet aggregation results. We sought to investigate the effect of relative centrifugal force (RCF) intensity on LTA results. METHODS: Ten healthy controls had venous blood drawn and centrifuged at 150, 200, 300, and 500 g for 10 min. Cell counts in whole blood and platelet-rich plasma (PRP) were measured using a hematology analyzer. LTA was performed using 1.0 µm adenosine diphosphate (ADP) and 0.4 µm epinephrine as an agonist. Aggregation (%) was compared at 60, 120, 180, and 300 s and at maximum aggregation. RESULTS: Centrifugation speed was associated with decreasing platelet count (P < 0.001) and decreasing mean platelet volume (P < 0.001) in PRP. Maximum aggregation decreased with increasing speeds for ADP 1.0 µm (150 g- 89%, 200 g- 93%, 300 g- 71%, 500 g- 17%; P < 0.001). Similar findings were noted at 120 s (150 g- 69%, 200 g- 50%, 300 g- 35%, 500 g- 12%; P < 0.001), 180 s (150 g- 82%, 200 g- 74%, 300 g- 44%, 500 g- 13%; P < 0.001), and 300 s (150 g- 85%, 200 g- 88%, 300 g- 55%, 500 g- 14%; P < 0.001). Consistently, platelet aggregation in response to epinephrine 0.4 µm decreased significantly with increasing centrifuge RCF at 60, 120, 180, 300 s and at maximum aggregation (P < 0.05 for each comparison). CONCLUSION: Our data demonstrate the importance of centrifugation speed in the interpretation of LTA results, supporting the need for standardization of centrifugation RCF in LTA protocols.

Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis.

AIM: To determine whether an association exists between mean platelet volume (MPV) and acute myocardial infarction (AMI) and other cardiovascular events. Platelet activity is a major culprit in atherothrombotic events. MPV, which is widely available in clinical practice, is a potentially useful biomarker of platelet activity in the setting of cardiovascular disease. METHODS AND RESULTS: We performed a systematic review and meta-analysis investigating the association between MPV and AMI, all-cause mortality following myocardial infarction, and restenosis following coronary angioplasty. Results were pooled using random-effects modeling. Pooled results from 16 cross-sectional studies involving 2809 patients investigating the association of MPV and AMI indicated that MPV was significantly higher in those with AMI than those without AMI [mean difference 0.92 fL, 95% confidence interval (CI) 0.67-1.16, P < 0.001). In subgroup analyses, significant differences in MPV existed between subjects with AMI, subjects with stable coronary disease (P < 0.001), and stable controls (P < 0.001), but not vs. those with unstable angina (P = 0.24). Pooled results from three cohort studies involving 3184 patients evaluating the risk of death following AMI demonstrated that an elevated MPV increased the odds of death as compared with a normal MPV (11.5% vs. 7.1%, odds ratio 1.65, 95% CI 1.12-2.52, P = 0.012). Pooled results from five cohort studies involving 430 patients who underwent coronary angioplasty revealed that MPV was significantly higher in patients who developed restenosis than in those who did not develop restenosis (mean difference 0.98 fL, 95% CI 0.74-1.21, P < 0.001). CONCLUSIONS: Elevated MPV is associated with AMI, mortality following myocardial infarction, and restenosis following coronary angioplasty. These data suggest that MPV is a potentially useful prognostic biomarker in patients with cardiovascular disease. Whether the relationship is causal, and whether MPV should influence practice or guide therapy, remains unknown.

Behavioral and neurophysiological correlates of episodic coding, proactive interference, and list length effects in a running span verbal working memory task.

Updating refers to (1) discarding items from, (2) repositioning items in, and (3) adding items to a running working memory span. Our behavioral and fMRI experiments varied three factors: trial length, proactive interference (PI), and group integrity. Group integrity reflected whether the grouping of items at the encoding stage was violated at discarding. Behavioral results were consistent with the idea that updating processes have a relatively short refractory period and may not fatigue, and they revealed that episodic information about group context is encoded automatically in working memory stimulus representations. The fMRI results did not show evidence that updating requirements in a task recruit executive control processes other than those supporting performance on nonupdating trials. They did reveal an item-accumulation effect, in which signal increased monotonically with the number of items presented during the trial, despite the insensitivity of behavioral measures to this factor. Behavioral and fMRI correlates of PI extended previous results and rejected an alternative explanation of PI effects in working memory.

Activity in human frontal cortex associated with spatial working memory and saccadic behavior.

We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).

Functional neuroanatomical double dissociation of mnemonic and executive control processes contributing to working memory performance.

We used event-related functional MRI to investigate the neural bases of two categories of mental processes believed to contribute to performance of an alphabetization working memory task: memory storage and memory manipulation. Our delayed-response tasks required memory for the identity and position-in-the-display of items in two- or five-letter memory sets (to identify load-sensitive regions) or memory for the identity and relative position-in-the-alphabet of items in five-letter memory sets (to identify manipulation-sensitive regions). Results revealed voxels in the left perisylvian cortex of five of five subjects showing load sensitivity (as contrasted with alphabetization-sensitive voxels in this region in only one subject) and voxels of dorsolateral prefrontal cortex in all subjects showing alphabetization sensitivity (as contrasted with load-sensitive voxels in this region in two subjects). This double dissociation was reliable at the group level. These data are consistent with the hypothesis that the nonmnemonic executive control processes that can contribute to working memory function are primarily prefrontal cortex-mediated whereas mnemonic processes necessary for working memory storage are primarily posteriorly mediated. More broadly, they support the view that working memory is a faculty that arises from the coordinated interaction of computationally and neuroanatomically dissociable processes.

Antibodies to chondroitin sulfate C: a new detection assay and correlations with neurological diseases.

Antibodies to chondroitin sulfate C (ChS C) have been previously associated with sensory axonal neuropathy. Investigation of these antibodies has, however, been limited by the lack of a sensitive and reliable test for their detection. We developed a new enzyme-linked immunoassorbent assay (ELISA), where biotinylated ChS C was made to adhere to avidin-coated microwells. The new ELISA showed a much greater sensitivity than other currently available ELISAs for detection of anti-ChS C antibodies. A total of 480 sera (466 patients and 14 normal volunteers) were tested at increasing dilutions for anti-ChS C antibody activity. Normal subjects had IgM anti-ChS C antibody titers of up to 3,200 and mildly elevated titers of 6,400 were seen in a variety of diseases. Eleven patients had titers of 12,800 or higher. These included seven patients with sensory axonal neuropathy, three with amyotrophic lateral sclerosis and one with corticobasal ganglionic degeneration. These studies indicate that anti-ChS antibodies do occur in patients with axonal sensory neuropathy, but are not limited to that disease.

Stabilization of helical peptides by mixed spaced salt bridges.

Whether or not surface salt bridges have a strong stabilizing effect on the native structure in proteins remains uncertain. Previous studies of model peptides have shown that salt bridges spaced at i,i +4 along the chain are more stabilizing than those spaced at i,i +3, with a preference for the order acid-base rather than base-acid from N to C terminus. An analysis of the effect of spacing the ion pairs in short helical peptides is presented, in which acidic and basic side chains spaced two or three residues apart alternate along the chain. The mixed spacing proves to be stabilizing relative to pure spacings. A control peptide in which salt bridges were spaced uniformly three residues apart proved to form a beta-sheet structure rather than alpha-helix. This is due to formation of a silk-like apolar face consisting of alanine side chains; the mesoscopic structure formed by these sheets can be imaged by scanning microscopy.

The mandibular repositioning device: role in the treatment of obstructive sleep apnea.

The role of oral appliances in the routine treatment of obstructive sleep apnea (OSA) is not well defined. This prospective study attempts to clarify the clinical role of a specific oral appliance, the mandibular repositioning device (MRD). This study evaluated the demographic, polysomnographic, and cephalometric radiographic findings predictive of treatment success or failure with the MRD. Twenty-nine patients were diagnosed with mild to severe OSA by nocturnal polysomnography. The majority of these patients were intolerant to nasal continuous positive airway pressure (CPAP) and all were fitted with a MRD. Twenty-three of these patients were compliant initially with MRD use and received post-treatment nocturnal polysomnogrpahy at a mean of 104 days after receiving the device. The respiratory disturbance index (RDI) decreased with MRD use (37 +/- 23 versus 18 +/- 20 events/hour, p < 0.001), and 16 of the 23 patients (69%) were considered responders (decrease in RDI > or = 50% and posttreatment RDI < or = 20). Measurements of subjective and objective daytime sleepiness, nocturnal oxygen desaturation, and snoring were all improved with MRD use. A pre-treatment RDI > 40 was present in four of the seven (67%) non-responders. Age, body mass index, and cephalometric radiographic measurements were not predictive of treatment outcome. Sixteen of 23 patients (70%) continue to use the MRD after 3.4 +/- 0.7 years. This study suggests that the MRD is useful in the long-term treatment of patients with OSA of mild to moderate severity.

Poly(adenosine diphosphoribose) polymerase in peripheral blood leukocytes from normal donors and patients with malignancies.

A two-color flow cytometric technique was developed to analyze poly(ADP-ribose) polymerase (PADPRP) in different individuals as a function of different physiological or pathological conditions and to establish the basis for determining whether enzyme deficiency may predispose to degenerative or malignant disorders. Peripheral blood granulocytes were devoid of enzyme activity, whereas mononuclear cells had variable amounts. PADPRP was highest in B cells, intermediate in T cells, and lowest in monocytes. This pattern of enzyme distribution and relative enzyme content of different types of cells was remarkably constant in normal subjects. In a series of 66 normal donors there was no significant biological variation in enzyme content as a function of age, race, or sex. The mean PADPRP values in peripheral blood mononuclear cells from 81 random patient samples obtained from an ambulatory oncology clinic did not differ significantly from normal subjects. However, groups of patients with breast cancer, lymphocytic malignancies, and esophageal cancer were observed to have below normal levels for peripheral blood mononuclear cell PADPRP.

Cyclosporine induces abnormal facial bone growth in children: a preliminary study.

Using cephalometric radiography, facial bony structure of a group of pediatric renal transplant recipients immunosuppressed with cyclosporine (CsA) and prednisone was studied and compared with a control group of children. A pattern of abnormal facial growth was demonstrated on cephalometry in eight of nine transplant recipients receiving CsA. The abnormalities included shortening of posterior facial height and increased anterior facial height with a deep mandibular plane angle. There was also an absolute shortening in the mandibular body and mandibular retrognathia. These findings may be consistent with inhibition of mandibular condylar growth inhibiting the anteroinferior growth of the mandible. Similar changes were present in two children with end-stage renal disease and none of the remaining nine control patients (P less than 0.01, chi-squared analysis). The affected area appears to be the lower third of the face. The role of CsA in affecting facial bony growth in children needs to be evaluated further.

Alveolar atrophy and decreased skeletal mass of the radius.

Using absorptiometry, the bone calcium mass (BCM) at two different sites of the radius was measured in 12 male patients referred for vestibuloplasty of the mandible. The most distal site contained both cortical and cancellous bone while the other site contained cortical bone only. The BCM values were compared with those for normal patients of the same age. The patients with mandibular atrophy all had less bone in the radius than their age-matched controls (p less than 0.01). This is indicative of a systemic factor or factors operating both in the mandible and in the radius. The examination prior to oral surgery should therefore include an evaluation for diseases causing general bone loss.

Adenoid cystic carcinoma of the parotid gland: report of case.

A case of adenoid cystic carcinoma of the parotid gland is reported, in which the initial symptom was facial paresthesia. Pathologic features, treatment, and prognosis of the tumor have been discussed.

Interpositional bone graft augmentation of the atrophic mandible: a preliminary report.

The mandible is sectioned in an oblique direction and an iliac crest graft is placed between the fragments for augmentation of an atrophied mandible. The technique was used in 12 patients; follow-up examinations included serial panoramic radiographs and recording of changes in mandibular height. A 10% to 27% loss of the height gained occurred between three and 12 months postoperatively.