Unique Barcoded Primer-Assisted Sample-Specific Pooled Testing (Uni-Pool) for Large-Scale Screening of Viral Pathogens.

Pooled testing has been widely adopted recently to facilitate large-scale community testing during the COVID-19 pandemic. This strategy allows to collect and screen multiple specimen samples in a single test, thus immensely saving the assay time and consumable expenses. Nevertheless, when the outcome of a pooled testing is positive, it necessitates repetitive retesting steps for each sample which can pose a serious challenge during a rising infection wave of increasing prevalence. In this work, we develop a unique barcoded primer-assisted sample-specific pooled testing strategy (Uni-Pool) where the key genetic sequences of the viral pathogen in a crude sample are extracted and amplified with concurrent tagging of sample-specific identifiers. This new process improves the existing pooled testing by eliminating the need for retesting and allowing the test results-positive or negative-for all samples in the pool to be revealed by multiplex melting curve analysis right after real-time polymerase chain reaction. It significantly reduces the total assay time for large-scale screening without compromising the specificity and detection sensitivity caused by the sample dilution of pooling. Our method was able to successfully differentiate five samples, positive and negative, in one pool with negligible cross-reactivity among the positive and negative samples. A pooling of 40 simulated samples containing severe acute respiratory syndrome coronavirus-2 pseudovirus of different loads (min: 10 copies/µL; max: 103 copies/µL) spiked into artificial saliva was demonstrated in eight randomized pools. The outcome of five samples in one pool with a hypothetical infection prevalence of 15% in 40 samples was successfully tested and validated by a typical Dorman-based pooling.

Influences on emergency department attendance among frail older people with deteriorating health: a multicentre prospective cohort study.

OBJECTIVES: To examine the patterns and influences on repeated emergency department attendance among frail older people with deteriorating health. STUDY DESIGN: Multicentre prospective cohort study (International Access Rights and Empowerment II study) with convergent mixed methods design. METHODS: Eligible patients were aged ≥65 years, with Clinical Frailty Score ≥5, and ≥1 hospital admission or ≥2 acute attendances in the previous 6 months. Questionnaires were administered to participants over 6 months and we extracted clinical data from the medical records. We conducted modified Poisson multivariable regression analysis to identify factors associated with repeated emergency department attendance (≥2 over 6 months) and thematic analysis of qualitative interviews. RESULTS: A total of 90 participants were recruited. The mean age was 84 years, and 63% were women. Of 87 participants, 21 experienced repeated emergency department attendance. Severe and/or overwhelming pain (adjusted prevalence ratio 2.44, 95% confidence interval 1.17-5.11), greater number of comorbidities (1.32, 1.08-1.62), ≥10 community nursing contacts (2.93, 1.31-6.56), and a total of ≥2 weeks spent in hospital during the previous 6 months (2.91, 1.24-6.84) were associated with repeated attendance. From 45 interviews, we identified influences on emergency department attendance: 1. inaccessibility of community healthcare; 2. perceived barriers to community healthcare seeking; 3. perceived benefits of hospital admission; 4. barriers to recovery during previous hospital admission (unsuitable food, inactivity); and 5. poorly coordinated transitions between settings. CONCLUSIONS: We identified missed opportunities to optimise older people's recovery during hospital admission, such as improved food and a timely and coordinated discharge, which may reduce reattendances. Proactive care in the community with systematic assessment of symptoms may be required, particularly for those with multimorbidity.

Oligonucleotide hybridization with magnetic separation assay for multiple SNP phasing.

Since humans have two copies of each gene, multiple mutations in different loci may or may not be found on the same strand of DNA (i.e., inherited from one parent). When a person is heterozygous at more than one position, the placement of these mutations, also called the haplotype phase, (i.e., cis for the same strand and trans for different strands) can result in the expression of different amount and type of proteins. In this work, we described an enzyme-free method to phase two single nucleotide polymorphisms (SNPs) using two fluorophore/quencher-labelled probes, where one of which was biotinylated. The fluorescence signal was obtained twice: first, after the addition of the labelled probes and second, after the addition of the magnetic beads. The first signal was shown to be proportional to the total number of SNP A and SNP B present in the target analyte, while the second signal showed a marked decrease of the fluorescence signal from the non-biotinylated probe when the SNPs were in trans, showing that the probe immobilized on the magnetic bead selectively captures targets with SNPs in a cis configuration. We then mimic the nature of the human genome which consists of two haplotype copies of each gene, and showed that 250 nM of the 10 possible pairs of haplotypes could be differentiated using a combination of fluorescence microscopy and fluorescence detection.

Toehold probe-based interrogation for haplotype phasing of long nucleic acid strands.

The arrangement of multiple single nucleotide polymorphisms (SNPs) in a gene, called a haplotype phase, is increasingly recognized as critical for accurate determination of disease risk and severity. However, conventional toehold-mediated strand displacement reactions are only able to interrogate SNPs, but not phase them since it is not known whether two SNPs in the same copy of the gene (cis) or in different copies of the same gene (trans) will give the same readout. While the rational introduction of an enzyme enables haplotype phasing, the complicated and stable secondary structure of long, single-stranded DNA sequences at room temperature limits its use. Complex nucleic acid structures make the hybridization of the probes difficult. Thus, we designed a molecular method to reveal the relative positions of SNPs located 1.4 kb apart in two copies of a gene by employing a competitive toehold probes and sink strategy at an elevated temperature. As such, we have successfully differentiated 20 nM of the 10 possible diplotypes in a long DNA target with two SNP sites located 1.4 kb apart within an hour without any additional amplification step. This offers a promising technology for accurate and fast haplotype phasing of SNPs that are over multiple kilobases away from each other.

Iron-Insensitive Quantitative Assessment of Subcortical Gray Matter Demyelination in Multiple Sclerosis Using the Macromolecular Proton Fraction.

BACKGROUND AND PURPOSE: Fast macromolecular proton fraction mapping is a recent quantitative MR imaging method for myelin assessment. The objectives of this study were to evaluate the macromolecular proton fraction as a measure of demyelination in subcortical GM structures in multiple sclerosis and assess a potential relationship between demyelination and excess iron deposition using the macromolecular proton fraction and T2* mapping. MATERIALS AND METHODS: Macromolecular proton fraction and T2* maps were obtained from 12 healthy controls, 18 patients with relapsing-remitting MS, and 12 patients with secondary-progressive MS using 3T MR imaging. Parameter values in the caudate nucleus, globus pallidus, putamen, substantia nigra, and thalamus were compared between groups and correlated to clinical data. RESULTS: The macromolecular proton fraction in all subcortical structures and T2* in the globus pallidus, putamen, and caudate nucleus demonstrated a significant monotonic decrease from controls to patients with relapsing-remitting MS and from those with relapsing-remitting MS to patients with secondary-progressive MS. The macromolecular proton fraction in all subcortical structures significantly correlated with the Expanded Disability Status Scale and MS Functional Composite scores with absolute Pearson correlation coefficient (r) values in a range of 0.4-0.6. Significant correlations (r = -0.4 to -0.6) were also identified between the macromolecular proton fraction and the 9-Hole Peg Test, indicating a potential relationship with nigrostriatal pathway damage. Among T2* values, weak significant correlations with clinical variables were found only in the putamen. The macromolecular proton fraction did not correlate with T2* in any of the studied anatomic structures. CONCLUSIONS: The macromolecular proton fraction provides an iron-insensitive measure of demyelination. Myelin loss in subcortical GM structures in MS is unrelated to excess iron deposition. Subcortical GM demyelination is more closely associated with the disease phenotype and disability than iron overload.

Kinetically-enhanced DNA detection via multiple-pass exonuclease III-aided target recycling.

One of the promising approaches to address the challenge of detecting dilute nucleic acid analytes is exonuclease III-aided target recycling. In this strategy, the target DNA self-assembles with the reactant DNA probes and displays itself as a reactant and product at the same time. This provides an autonomous mechanism to release and reuse the analyte from each round of reactions for repetitive cycles, which amplifies the signal without amplifying the analyte itself. However, for very low amounts of the analyte, it takes a considerably long time before a detectable signal is generated. Thus, in this paper, we report a kinetically-enhanced target recycling strategy by designing two more target recycling sub-reactions that are triggered by the byproducts of the first reaction involving the target analyte. In this manner, concentrations of up to 0.5 pM of target DNA can be detected in 15 minutes.

Conditional Displacement Hybridization Assay for Multiple SNP Phasing.

The two chromosomal copies of the human genome are highly polymorphic, and the allelic content on each strand can dictate a person's biological outcomes. While many of the current diagnostic tools are able to detect the presence of multiple mutations at the same time, most cannot determine the phase of these mutations unless long-range PCR or sequencing techniques are used or if templates are compartmentalized into single copies prior to amplification. Here, an enzyme-coupled hybridization assay, named conditional displacement hybridization assay (CDHA), is described for the concurrent and rapid determination of the presence and phase of SNP variants. In this approach, short DNA probes were utilized to first quantify the amount of SNPs on the templates using a two-channel fluorescence measurement. The hybrids formed between the probes and the templates then set up the right condition for the subsequent enzymatic displacement and quenching of a fluorophore-labeled strand, which happens only if both SNPs are present on the same strand. The drop in the fluorescence signal thereby indicates the phase of the two SNPs. As a proof of concept, we tested the assay on four variants of an arbitrary sequence-with or without mutation on two sites 100 nts apart. The assay described herein was able to determine the haplotype phase of the samples in less than 1 h. This method promises a direct, cost-effective, and laboratory-based test to extract further genetic information to determine and/or predict diseases and traits dependent on SNP phasing.

Dynamic changes in mitochondrial DNA, distribution and activity within cat oocytes during folliculogenesis.

Mitochondria play fundamental roles during oocyte development. The accumulation and spatial redistribution of these energy-producing organelles have been linked to the developmental competence of mammalian oocytes. Here, we assessed the copy number, distribution and activity of mitochondria within cat oocytes during folliculogenesis. In Experiment 1, oocytes were recovered from primordial (n = 152), primary (112), secondary (95), early (131), small (118), antral (86) and advanced antral (5) stages follicles, and mitochondria DNA extracted and quantified using qPCR. In Experiment 2, oocytes from pre-antral (n = 44), early antral (n = 66), small antral (n = 59), antral (n = 41) and advanced antral (n = 21) follicles were isolated and stained with CMXRos MitoTracker dye to assess mitochondrial distribution pattern and activity levels. Oocyte's mitochondria DNA (mtDNA) copy numbers gradually increased as folliculogenesis progressed, with a significant shift at the small antral stage (0.5 to <1 mm in diameter). The location of mitochondria gradually shifted from a homogeneous distribution throughout the cytoplasm in pre-antral oocytes to a pericortical concentration in the advanced antral stage. Quantification of CMXRos fluorescent intensity revealed a progressive increase in mitochondrial activity in oocytes from the pre-antral to the large antral follicles. Taken together, these findings demonstrated that cat oocytes undergo dynamic changes in mitochondrial copy number, distribution and activity during folliculogenesis. These significant modifications to this crucial cytoplasmic organelle are likely associated with the acquisition of developmental competency by cat oocytes.

Erratum to: Further analysis of selection-based instruction, lag reinforcement schedules, and the emergence of topography-based responses to interview questions.

[This corrects the article DOI: 10.1007/s40616-015-0031-5.].

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles.

UNLABELLED: Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study's research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after. IMPLICATIONS: The use of ultra-short-acting opioids may be an appropriate technique for infants less than 2 mo old when tracheal extubation after surgery is anticipated.

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis.

UNLABELLED: Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic. IMPLICATIONS: Abnormal breathing patterns can follow anesthesia in infants after surgical repair of pyloric stenosis. Occasionally, these patterns can be associated with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures.

UNLABELLED: Remifentanil hydrochloride is an ultra-short-acting opioid that undergoes rapid metabolism by tissue and plasma esterases. We aimed to characterize the pharmacokinetics and determine the hemodynamic profile of remifentanil after a single-bolus dose in children aged 0 to 18 yr. Forty-two children undergoing elective surgical procedures received remifentanil 5 microg/kg infused over 1 min. Patients were divided into age groups as follows: young infants (< or =2 mo), older infants (> 2 mo to < 2 yr), young children (2 to < 7 yr), older children (7 to < 13 yr), adolescents (13 to < 16 yr), and young adults (16 to < 18 yr). Arterial blood samples were collected and analyzed by mass spectroscopy to determine remifentanil pharmacokinetic profiles. Hemodynamic measurements for remifentanil's effect were made after the infusion. Methods of statistical analysis included analysis of variance and linear regression, with significance at P < or = 0.05. Complete remifentanil pharmacokinetic data were obtained from 34 patients. The volume of distribution was largest in the infants < 2 mo (mean, 452 mL/kg) and decreased to means of 223 to 308 mL/kg in the older patients. There was a more rapid clearance in the infants < 2 mo of age (90 mL. kg(-1). min(-1)) and infants 2 mo to 2 yr (92 mL. kg(-1). min(-1)) than in the other groups (means, 46 to 76 mL. kg(-1). min(-1)). The half-life was similar in all age groups, with means of 3.4 to 5.7 min. Seven subjects (17%) developed hypotension related to the remifentanil bolus. Remifentanil showed an extremely rapid elimination similar to that in adults. The fast clearance rates observed in neonates and infants, as well as the lack of age-related changes in half-life, are in sharp contrast to the pharmacokinetic profile of other opioids. Remifentanil in a bolus dose of 5 microg/kg may cause hypotension in anesthetized children. IMPLICATIONS: The pharmacokinetics of remifentanil were studied in children from birth to 18 yr. Remifentanil was found to have age-related changes in clearance and volume of distribution, but not half-life. The increased clearance observed in young infants is in contrast to other opioids.

A randomized, double-blinded study of remifentanil versus fentanyl for tonsillectomy and adenoidectomy surgery in pediatric ambulatory surgical patients.

UNLABELLED: We compared, in a double-blinded manner, the anesthetic maintenance and recovery properties of remifentanil with a clinically comparable fentanyl-based anesthetic technique in pediatric ambulatory surgical patients. Anesthesia was induced with either halothane or sevoflurane and nitrous oxide and oxygen. Patients were randomized (computer generated) to receive either remifentanil or fentanyl in a blinded syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 microg. kg(-1). min(-1)) was begun. In patients receiving fentanyl, a bolus (2 microg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children. IMPLICATIONS: This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children.

Estimation of jugular venous O2 saturation from cerebral oximetry or arterial O2 saturation during isocapnic hypoxia.

OBJECTIVE: Near-infrared spectroscopy (NIRS) has the potential for providing valuable information about oxygen delivery to the brain. However, questions have been raised about the accuracy of these measurements. This study was undertaken to compare noninvasive cerebral saturation measurements to jugular venous saturation under conditions of hypoxia and hypercapnia. METHODS: Data was obtain on forty-two subjects. Cerebral oxygenation was measured with a Somanetics INVOS 4100-SSA placed on the forehead of the subjects. PETCO2 was controlled to approximately 2 and 7 mmHg above resting values and PETO2 was controlled to 80, 45, 60 and 41 mmHg consecutively for four of five minutes each. Internal jugular blood gas measurements were made via a retrograde catheter. RESULTS: Both the cerebral oximetry measured saturation (rSO2) and the jugular venous saturation (SjvO2) were significantly increased by increasing the PETCO2 at all levels of hypoxia. The increase in the rSO2 was less than the increase in SjvO2. The rSO2 had a bias of 5.2% and a precision of 10.7% compared to the measured SjvO2. DISCUSSION: Cerebral oxygen saturation measured by cerebral oximetry compares well to the measured SjvO2 in normal subjects, despite multiple physiological reasons for differences. The closer relationship of SjvO2 to rSO2 than SaO2 under the conditions of these experiments indicates that the measurement reflects primarily intracranial saturation. However, outcome studies under clinical conditions are needed to determine the clinical utility of cerebral oximetry.

The role of psychopathology in the parenting of drug-dependent women.

This paper explores the parenting of drug-dependent women and the contributions of comorbid psychopathology to their parenting. A sample of 32 children whose mothers were dependent on opioid drugs during pregnancy and 37 children whose mothers were not drug users were followed from birth to middle childhood. Multivariate regression analyses were conducted contrasting whether maternal substance abuse or psychopathology was more closely linked to parenting behaviors and continuity in parenting over time. Maternal drug dependence was related to whether mothers were able to remain primary caregivers for their children over time, even after controlling for psychopathology. Maternal drug use was related to unresponsive and negative parenting behavior during mother-infant interaction, but this relation was largely accounted for by the effects of comorbid maternal psychopathology on parenting, particularly symptoms of antisocial and related personality disorders. For those children whose mothers continued to care for them into middle childhood, perceptions of their mothers as rejecting were related to maternal antisocial personality and maternal depression. Substance-abuse treatment for women should be integrated with interventions addressing their mental health and parenting needs.

Effects of alfentanil on the ventilatory response to sustained hypoxia.

BACKGROUND: The ventilatory response to acute hypoxia is biphasic, with an initial rapid increase followed by a slower decline. In humans, there is evidence that the magnitude of the decline in ventilation is proportional to the size of the initial increase. This study was done to define the role of exogenous opioids in the ventilatory decline seen with prolonged hypoxia. METHODS: Ten healthy persons were exposed to isocapnic hypoxia for 25 min, followed by 5 min of isocapnic normoxia and 5 min of isocapnic hypoxia. These conditions were repeated during a computer-controlled alfentanil infusion. RESULTS: Serum alfentanil levels were constant among the volunteers (38+/-12 ng/ml). Alfentanil decreased both the initial and second acute hypoxic responses (from 1.27+/-0.73 to 0.99+/-0.39 l x min(-1) x %(-1), P < 0.05; and from 0.99+/-0.70 to 0.41+/-0.29 l x min(-1) x %(-1), P < 0.05, respectively). The magnitude of the decrease in ventilation during the 25 min of hypoxia was not changed (10+/-3.3 l/min for control; 12.3+/-7.5 l/min for alfentanil). CONCLUSIONS: Alfentanil reduced the acute ventilatory response to hypoxia. The absolute value of hypoxic ventilatory decline was not increased, but a measure of residual hypoxic ventilatory decline (the ratio of ventilation between the second and first steps into hypoxia) was decreased, which supports the hypothesis that opioids potentiate centrally mediated ventilatory decline.

Accuracy of a cerebral oximeter in healthy volunteers under conditions of isocapnic hypoxia.

BACKGROUND: A cerebral oximeter measures oxygen saturation of brain tissue noninvasively by near infrared spectroscopy. The accuracy of a commercially available oximeter was tested in healthy volunteers by precisely controlling end-tidal oxygen (P[ET]O2) and carbon dioxide (P[ET]CO2) tensions to alter global cerebral oxygen saturation. METHODS: In 30 healthy volunteers, dynamic end-tidal forcing was used to produce step changes in P[ET]O2 resulting in arterial saturation ranging from approximately 70% to 100% under conditions of controlled normocapnia (each person's resting P[ET]CO2) or hypercapnia (resting plus 7-10 mmHg). Blood arterial (SaO2) and jugular bulb venous (S[jv]O2) saturations during each P(ET)O2 interval were determined by co-oximetry. The cerebral oximeter reading (rSO2) and an estimated jugular venous saturation (S[jv]O2), derived from a combination of SaO2 and rSO2, were compared with the measured S(jv)O2. RESULTS: The S(jv)O2 was significantly higher with hypercapnia than with normocapnia for the same SaO2. The rSO2 and S(jv)O2 were both highly correlated with S(jv)O2 for individual volunteers (mean r2 = 0.91 for each relation); however, the slopes and intercepts varied widely among volunteers. In three of them, the cerebral oximeter substantially underestimated the measured S(jv)O2. CONCLUSIONS: During isocapnic hypoxia in healthy persons, cerebral oxygenation as estimated by near infrared spectroscopy precisely tracks changes in measured S(jv)O2 within individuals, but the relation exhibits a wide range of slopes and intercepts. Therefore the clinical utility of the device is limited to situations in which tracking trends in cerebral oxygenation would be acceptable.

Unindicated preoperative testing: ASA physical status and financial implications.

STUDY OBJECTIVE: To determine if the ordering of unindicated preoperative laboratory tests is different for healthy (ASA physical status I and II) versus sicker (ASA physical status III) patients, and to examine the financial implications at our institution of unindicated preoperative testing. DESIGN: Prospective, cross-sectional study. SETTING: University hospital. PATIENTS: 383 consecutive patients scheduled for elective surgery and seen by an anesthesiologist in the Preoperative Clinic. Complete data was available for 312 patients. MEASUREMENTS AND MAIN RESULTS: Preoperative laboratory tests ordered by the surgeon were compared to those tests considered indicated by one of several anesthesiologists for ASA physical status I and II versus ASA physical status III patients. An average of 72.5% of tests ordered by surgeons were considered not indicated by the anesthesiologists. ASA physical status III patients had significantly fewer unindicated complete blood count, platelet count, prothrombin time, partial thromboplastin time, chemistry 12 profile, and chest radiography orders than did ASA physical status I and II patients. Our hospital could generate approximately $80,000 in variable and semifixed cost savings by eliminating these unindicated preoperative tests for the 5,100 patients seen in Preoperative Clinic annually (29% of the total surgical patients). CONCLUSIONS: A large percentage of preoperative tests ordered by surgeons at our institution are not indicated. Eliminating unindicated tests would cut hospital revenues in a climate where testing is fee-for-service and would save the hospital money in a managed-care or capitated system.

A randomized multicenter study of remifentanil compared with alfentanil, isoflurane, or propofol in anesthetized pediatric patients undergoing elective strabismus surgery.

Remifentanil hydrochloride is a new, ultrashort-acting opioid metabolized by nonspecific plasma and tissue esterases. We conducted this multicenter study to examine the hemodynamic response and recovery profile of premedicated children undergoing strabismus repair who were randomly assigned to receive one of four treatment drugs (remifentanil, alfentanil, isoflurane, or propofol) along with nitrous oxide and oxygen for maintenance of anesthesia. Induction of anesthesia was by nitrous oxide, oxygen, and halothane or nitrous oxide, oxygen, and propofol. Anesthesia was then maintained with remifentanil 1.0 microgram/kg over 30-60 s, followed by a constant infusion of 1.0 microgram.kg-1.min-1, alfentanil 100 micrograms/kg bolus followed by a constant infusion of 2.5 micrograms.kg-1.min-1, propofol 2.5 mg/kg bolus followed by a constant infusion of 200 micrograms.kg-1.min-1, or isoflurane 1.0 minimum alveolar anesthetic concentration. The infusions of the anesthetics and the administration of the inhaled gases were adjusted clinically by predetermined protocols. Elapsed time intervals from the end of surgery to the time the patients were tracheally extubated and displayed purposeful movement, as well as the time the patients met the postanesthesia care unit (PACU) and hospital discharge times, were recorded. Heart rate and systolic and diastolic blood pressure were measured at fixed intervals. In addition, cardiovascular side effects (bradycardia, hypotension, and hypertension) as well as vomiting, pruritus, agitation, and postoperative hypoxemia were also noted. There were no significant differences in patient demographics among the treatment groups. There was no difference in the early recovery variables (times to extubation and purposeful movement) or the times to PACU and hospital discharge among groups. There were significant differences in side effects among the groups. Patients who received remifentanil had higher PACU objective pain-discomfort scores than those who received alfentanil and propofol. Patients anesthetized with alfentanil had a greater incidence in the use of naloxone and a greater incidence of postoperative hypoxemia compared with those anesthetized with remifentanil. The incidence of postoperative hypoxemia was the same for remifentanil, propofol, and isoflurane groups. There were no significant differences in the incidence of emesis among the four groups, and all four groups had similar hemodynamic profiles. We conclude that remifentanil appears to be an effective drug for anesthesia. Its hemodynamic and recovery profile appear similar to other comparable drugs. Based on previous pharmacokinetic studies, the 1.0 microgram.kg-1.min-1 infusion may be twice the 50% effective dose observed in adults. In this study, the relative "overdose" of remifentanil was well tolerated and did not prolong recovery.