Carbetocin vs. oxytocin at elective caesarean delivery: a double-blind, randomised, controlled, non-inferiority trial of low- and high-dose regimens.

Carbetocin or oxytocin are given routinely as first-line uterotonic drugs following delivery of the neonate during caesarean delivery to prevent postpartum haemorrhage. Low doses may be as effective as high doses with a potential reduction in adverse effects. In this double-blind, randomised, controlled, non-inferiority trial, we assigned low-risk patients undergoing elective caesarean delivery under spinal anaesthesia to one of four groups: carbetocin 20 µg; carbetocin 100 µg; oxytocin 0.5 IU bolus + infusion; and oxytocin 5 IU bolus + infusion. The study drug was given intravenously after delivery of the neonate. Uterine tone was assessed by the obstetrician 2, 5 and 10 minutes after study drug administration according to an 11-point verbal numerical rating scale (0 = atonic, 10 = excellent tone). The primary outcome measure was uterine tone 2 min after study drug administration. The pre-specified non-inferiority margin was 1.2 points on the 11-point scale. Secondary outcomes included uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects. Data were available for 277 patients. Carbetocin 20 µg resulting in uterine tone of (median (IQR [range])) 8 (7-8 [1-10]) was non-inferior to carbetocin 100 µg with tone 8 (7-9 [3-10]), median (95%CI) difference 0 (-0.44-0.44). Similarly, oxytocin 0.5 IU with tone 7 (6-8 [3-10]) was non-inferior to oxytocin 5 IU with tone 8 (6-8 [2-10]), median (95%CI) difference 1 (0.11-1.89). Carbetocin 20 µg was also non-inferior to oxytocin 5 IU, and oxytocin 0.5 IU was non-inferior to carbetocin 100 µg. Uterine tone after 5 and 10 minutes, use of additional uterotonics, blood loss and adverse effects were similar in all groups.

Learning design in science education: perspectives from designing a graduate-level course in evidence-based teaching of science.

Graduate students intending to pursue an academic career in the sciences have much to gain by learning to teach science but often have limited training opportunities. In response to this need, we designed a one-semester course, Learning Design in Science Education (LDSE), in which students receive formal training in pedagogical theory with role model demonstration of current best practices in active learning. Building from previous descriptions of similar courses, we added a practical experience for the students to utilize their new skills to design and teach a mini science course at the end of the semester. Additionally, students developed a teaching portfolio, complete with a personal teaching statement, syllabus, course materials, and evaluations from peers and faculty. Overall, the course was well received by the students and there are early indications that students benefited from their participation in the course. In this manuscript, we present the design and outcomes of the course, faculty and student perceptions, and thoughts on improvements for future semesters and its potential for use by others.NEW & NOTEWORTHY The need for graduate students and other trainees to learn effective methods for teaching science is greater than ever. In this manuscript, we offer a model course for the training of graduate students in learning theory, curriculum design, and technology use in a biomedical sciences environment.

Well-documented benign sonographic characteristics are rarely seen in malignant masses: is now the time to biopsy less?

AIM: To determine whether malignant breast masses demonstrate any of the eight well-documented benign criteria on ultrasound (US) to ascertain whether patients that display these characteristics can safely be discharged without intervention reducing the number of unnecessary benign biopsies. MATERIALS AND METHODS: A retrospective evaluation was performed of the US images of 816 histologically confirmed breast cancer cases diagnosed from 2016-2018. The malignant lesions were subdivided into seven age categories and compliance with the eight benign (Stavros) characteristics assessed. RESULTS: None of the 816 malignancies displayed all eight of the described benign Stavros characteristics. The combination of a smooth/well-circumscribed border and an ellipsoid shape with horizontal orientation in addition to being homogeneously isoechoic with three or less gentle lobulations was found in only 0.4% of cases (3/816). CONCLUSIONS: This research adds to the body of literature supporting the robust nature of the Stavros criteria and supports the non-invasive management of lesions that display all of these associated benign features on US. The presence of established benign ultrasound characteristics are very uncommonly seen in malignancies as highlighted in this study, and it is proposed than no breast cancers will display all eight criteria combined. It is suggested that adherence to the well-documented benign characteristics when assessing solid breast lesions could safely obviate the need for biopsy in women of all ages.

Oxytocin at elective caesarean delivery: a dose-finding study in women with obesity.

Prophylactic oxytocin administration at the third stage of labour reduces blood loss and the need for additional uterotonic drugs. Obesity is known to be associated with an increased risk of uterine atony and postpartum haemorrhage. It is unknown whether women with obesity require higher doses of oxytocin in order to achieve adequate uterine tone after delivery. The purpose of this study was to establish the bolus dose of oxytocin required to initiate effective uterine contraction in 90% of women with obesity (the ED90 ) at elective caesarean delivery. We conducted a double-blind dose-finding study using the biased coin up-down design method. Term pregnant women with a BMI ≥ 40 kg.m-2 undergoing elective caesarean delivery under regional anaesthesia were included. Those with conditions predisposing to postpartum haemorrhage were not included. Oxytocin was administered as an intravenous bolus over 1 minute upon delivery of the fetus. With the first woman receiving 0.5 IU, oxytocin doses were administered according to a sequential allocation scheme. The primary outcome measure was satisfactory uterine tone, as assessed by the operating obstetrician 2 minutes after administration of the oxytocin bolus. Secondary outcomes included the need for rescue uterotonic drugs, adverse effects and estimated blood loss. We studied 30 women with a mean (SD) BMI of 52.3 (7.6) kg.m-2 . The ED90 for oxytocin was 0.75 IU (95%CI 0.5-0.93 IU) by isotonic regression and 0.78 IU (95%CI 0.68-0.88 IU) by the Dixon and Mood method. Our results suggest that women with a BMI ≥ 40 kg.m-2 require approximately twice as much oxytocin as those with a BMI < 40 kg.m-2 , in whom an ED90 of 0.35 IU (95%CI 0.15-0.52 IU) has previously been demonstrated.

Carbetocin at elective caesarean section: a sequential allocation trial to determine the minimum effective dose in obese women.

Postpartum haemorrhage is a leading cause of maternal death during childbirth. There is an increasing incidence of atonic postpartum haemorrhage in developed countries, and maternal obesity has been proposed as a contributing factor. The dose-response relationship of carbetocin in obese women has not yet been determined. We conducted a double-blind, dose-finding study of carbetocin using a biased coin up-and-down design in women with a body mass index ≥ 40 kg.m-2 undergoing elective caesarean section. The determinant for a successful response was satisfactory uterine tone, with no intra-operative need for additional uterotonic drugs. Secondary outcomes included the use of additional uterotonic drugs postoperatively, estimated blood loss and adverse effects of carbetocin administration. Thirty women were recruited to the study. The median (IQR [range]) body mass index was 44.93 (41.5-55.2 [40-66.5]) kg.m-2 . The ED90 of carbetocin was estimated as 62.9 (95%CI 57.0-68.7) µg using the truncated Dixon and Mood method, and 68 (95%CI 52-77) µg using the isotonic regression method. The estimated blood loss was 880 (621-1178 [75-2442]) ml. The overall rates of hypotension and hypertension after delivery were 40% and 6.7%, respectively, while nausea occurred in 26.7% of women. The ED90 for carbetocin in obese women at elective caesarean section is lower than the dose of 100 µg currently recommended by the Society of Obstetricians and Gynaecologists of Canada, but is approximately four times higher than the previously demonstrated ED90 of 14.8 µg in women with body mass index < 40 kg.m-2 .

Uterotonics in elective caesarean delivery: a randomised non-inferiority study comparing carbetocin 20 µg and 100 µg.

Postpartum haemorrhage is the leading cause of maternal mortality worldwide and prophylactic uterotonic drug administration after the delivery of the infant is advised. Carbetocin is recommended as an uterotonic, but the minimum effective dose has not been verified. We compared the efficacy of two doses of intravenous carbetocin (20 µg and 100 µg) in women undergoing elective caesarean delivery. This was a randomised, double-blind, non-inferiority study in women at low risk of postpartum haemorrhage. Carbetocin was administered on delivery of the anterior shoulder of the neonate. Uterine tone was assessed by the obstetrician 2 min and 5 min after carbetocin administration according to an 11-point numerical rating scale (0 = atonic uterus and 10 = firm uterus). The primary outcome was uterine tone 2 min after carbetocin administration. The pre-specified non-inferiority margin was 1 point on the 11-point scale. Secondary outcomes included: uterine tone at 5 min; use of additional uterotonics within 24 h; blood loss; and adverse effects. Data were available for 53 women in the carbetocin-20 group and for 55 women in the carbetocin-100 group. The mean (SD) uterine tone at 2 min was 7.5 (1.9) in the carbetocin-20 group and 8.0 (1.5) in the carbetocin-100 group. The lower limit of the one-sided 95%CI for the mean difference was outside the non-inferiority margin (at -1.1; p = 0.11) meaning non-inferiority of carbetocin 20 µg compared with carbetocin 100 µg could not be confirmed. However, the secondary outcome measures of uterine tone at 5 min, blood loss and use of additional uterotonics were similar in both groups.

Determination of the optimal programmed intermittent epidural bolus volume of bupivacaine 0.0625% with fentanyl 2 µg.ml-1 at a fixed interval of forty minutes: a biased coin up-and-down sequential allocation trial.

The optimum time interval for 10 ml boluses of bupivacaine 0.0625% + fentanyl 2 µg.ml-1 as part of a programmed intermittent epidural bolus regimen has been found to be 40 min. This regimen was shown to be effective without the use of supplementary patient-controlled epidural analgesia boluses in 90% of women during the first stage of labour, although with a rate of sensory block to ice above T6 in 34% of women. We aimed to determine the optimum programmed intermittent epidural bolus volume at a 40 min interval to provide effective analgesia in 90% of women (EV90 ) during the first stage of labour, without the use of patient-controlled epidural analgesia. We performed a prospective double-blind dose-finding study using the biased coin up-and-down sequential allocation method in 40 women. The estimated EV90 was 11.0 (95%CI 10.0-11.7) ml with the isotonic regression method and 10.7 (95%CI 10.3-11.0) ml with the truncated Dixon and Mood method. Overall, 18 women had a sensory block above T6, and 37 women exhibited no motor block. No women required treatment for hypotension. In conclusion, it is not possible to reduce the programmed intermittent epidural bolus volume from 10 ml, used in our current regimen, without compromising the quality of analgesia. Using this regimen, a high proportion of women will develop a sensory block above T6.

Gastric ultrasound in the third trimester of pregnancy: a randomised controlled trial to develop a predictive model of volume assessment.

Bedside gastric ultrasonography can be performed reliably by anaesthetists to assess gastric content in the peri-operative period. We aimed to study the relationship between gastric cross-sectional area, assessed by ultrasound, and volumes of clear fluids ingested by pregnant women. We recruited 60 non-labouring third-trimester pregnant women in a randomised controlled and assessor-blinded study. A standardised scanning protocol of the gastric antrum was performed in the 45° semirecumbent and 45° semirecumbent-right lateral positions. Subjects were randomly allocated to drink one out of six predetermined volumes of apple juice (0 ml, 50 ml, 100 ml, 200 ml, 300 ml, 400 ml). Qualitative and quantitative assessments at a baseline period after an 8-h fast, and immediately after the drink, were used to establish the correlation between antral cross-sectional area and volume ingested. A predictive model to estimate gastric volume was developed. Antral cross-sectional area in the semirecumbent right lateral position significantly correlated with the ingested volume (Spearman rank correlation = 0.7; p < 0.0001). A cut-off value of 9.6 cm2 discriminated ingested volumes ≥ 1.5 ml.kg-1 with a sensitivity of 80%, a specificity of 66.7%, and an area under the curve of 0.82. A linear predictive model was developed for gastric volume based only on antral cross-sectional area (Volume (ml) = -327.1 + 215.2 × log (cross-sectional area) (cm2 )). We conclude that in pregnant women in the third trimester of gestation, the antral cross-sectional area correlates well with volumes ingested, and this cut-off value in the semirecumbent right lateral position discriminates high gastric volumes.

Interrater reliability of qualitative ultrasound assessment of gastric content in the third trimester of pregnancy.

BACKGROUND: Pulmonary aspiration of gastric contents in pregnant women undergoing general anaesthesia is one of the most feared complications in obstetric anaesthesia. Bedside gastric ultrasonography is a feasible imaging tool to assess the gastric content. The purpose of this study was to investigate the reliability of qualitative bedside assessment of the gastric content performed by anaesthesiologists on third trimester pregnant women. METHODS: Pregnant women (≥32 weeks gestational age) were randomized to undergo ultrasound (US) assessments of their stomach in a fasting state (>8 h), or after ingestion of clear fluids only, or solid food. Three anaesthesiologists trained in gastric ultrasonography performed the assessments using a low-frequency curved-array US transducer (5-2 MHz). Primary outcome of the study was the consistency of raters in diagnosing the correct status of the gastric content, which was used to determine the interrater reliability among the three anaesthesiologists. Secondary outcomes were overall proportion of correct and incorrect diagnoses and the specific proportions of correct diagnosis across the three gastric content groups. RESULTS: We analysed 32 pregnant women. The interrater reliability displayed a kappa statistic of 0.74 (bias corrected 95% CI: 0.68-0.84). The overall proportion of correct diagnosis was 87.5% (84 of 96). The odds of correct diagnosis for 'solid contents' were 16.7 times the odds for 'empty', and 14.3 times for 'clear fluid'. CONCLUSIONS: Our results show the consistency of the qualitative US assessment of gastric contents of pregnant women in the third trimester by anaesthesiologists. A kappa of 0.74 suggests substantial agreement in terms of interrater reliability for this diagnostic measurement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01564030.

Influencing surgical management in patients with carcinoma of the cervix using a T2- and ZOOM-diffusion-weighted endovaginal MRI technique.

BACKGROUND: Endovaginal MRI (evMRI) at 3.0-T with T2-weighted (T2-W) and ZOnal Oblique Multislice (ZOOM)-diffusion-weighted imaging (DWI) potentially improves the detection of stage Ia/Ib1 cervical cancer. We aimed to determine its sensitivity/specificity, document tumour-to-stromal contrast and establish the effect of imaging on surgical management. METHODS: Following ethical approval and written informed consent, 57 consecutive patients with suspected stage Ia/Ib1 cervical cancer underwent evMRI at 3.0-T using T2-W and ZOOM-DWI. Sensitivity/specificity were calculated against histopathology for two independent observers. Tumour-to-stromal contrast was determined on T2-W, and diffusion-weighted (b=800 s mm(-2)) images and apparent diffusion coefficients (ADCs) were recorded. In patients due for radical vaginal trachelectomy (RVT), change of surgical management based on imaging findings was documented. RESULTS: Sensitivity/specificity for detecting tumour was the following: reporting read 88.0/81.8%, anonymised read 92.0/81.8% (observer 1); 84.0/72.7% (observer2; median tumour volume=1.7 cm(3)). Intraobserver agreement was excellent (kappa=0.89) and the interobserver agreement was good (kappa=0.65). Tumour-to-stromal contrast was greater on ZOOM-DWI compared with T2-W images (3.35±2.36 vs 1.39±0.95; P<0.0004). Tumour and stromal ADCs were significantly different (P<0.00001). In 31 patients due for RVT, evMRI altered surgical management in 12 (38.7%) cases (10 cone-biopsy, 2 chemoradiotherapy). CONCLUSION: T2-W+ZOOM-DWI evMRI has high sensitivity/specificity for detecting stage Ia/Ib1 cervical tumours; in patients due for RVT, the surgical management was altered in ∼39%.

The association of shock index and haemoglobin variation with postpartum haemorrhage after vaginal delivery: a prospective cohort pilot study.

INTRODUCTION: Shock index and continuous non-invasive haemoglobin monitoring (SpHb) have both been proposed for the timely recognition of postpartum haemorrhage (PPH). We sought to determine, in parallel, the association of each of shock index and SpHb with blood loss after vaginal delivery. METHODS: Sixty-six women were recruited to this prospective observational study. Shock index and SpHb were recorded postpartum for 120 min. The association between each of shock index and SpHb with quantitative blood loss (QBL) at 30, 60 and 120 min postpartum was determined using linear mixed models. Area-under-the-receiver-operator-characteristic (AUROC) curves were constructed to evaluate the diagnostic ability of shock index and SpHb to detect PPH (defined as QBL ≥1000 mL). RESULTS: Shock index trend was associated with QBL over the first 30 min (r=0.37, P=0.002), but not over 60 or 120 min. There was an association of SpHb trend with QBL over the first 30 min (P=0.06), but not over 60 min (r=-0.32, P=0.009) or 120 min (r=-0.26, P=0.03). Maximum shock index within 60 min correlated with QBL (r=0.54, P <0.001) and was a predictor of PPH (P=0.0012, AUROC 0.796). Maximum change in SpHb within 60 min negatively correlated with QBL (r=-0.4, P <0.001) and was a predictor of PPH (P=0.048, AUROC 0.761). CONCLUSIONS: The trend of shock index and its peak values are associated with blood loss after vaginal delivery and are early indicators of PPH. Negative trend of SpHb is a late sign of PPH and has a weaker association with blood loss than shock index.

CT diagnosis of ilioinguinal lymph node metastases in melanoma using radiological characteristics beyond size and asymmetry.

BACKGROUND: Diagnosis of lymph node (LN) metastasis in melanoma with non-invasive methods is challenging. The aim of this study was to evaluate the diagnostic accuracy of six LN characteristics on CT in detecting melanoma-positive ilioinguinal LN metastases, and to determine whether inguinal LN characteristics can predict pelvic LN involvement. METHODS: This was a single-centre retrospective study of patients with melanoma LN metastases at a tertiary cancer centre between 2008 and 2016. Patients who had preoperative contrast-enhanced CT assessment and ilioinguinal LN dissection were included. CT scans containing significant artefacts obscuring the pelvis were excluded. CT scans were reanalysed for six LN characteristics (extracapsular spread (ECS), minimum axis (MA), absence of fatty hilum (FH), asymmetrical cortical nodule (CAN), abnormal contrast enhancement (ACE) and rounded morphology (RM)) and compared with postoperative histopathological findings. RESULTS: A total of 90 patients were included. Median age was 58 (range 23-85) years. Eighty-eight patients (98 per cent) had pathology-positive inguinal disease and, of these, 45 (51 per cent) had concurrent pelvic disease. The most common CT characteristics found in pathology-positive inguinal LNs were MA greater than 10 mm (97 per cent), ACE (80 per cent), ECS (38 per cent) and absence of RM (38 per cent). In multivariable analysis, inguinal LN characteristics on CT indicative of pelvic disease were RM (odds ratio (OR) 3.3, 95 per cent c.i. 1.2 to 8.7) and ECS (OR 4.2, 1.6 to 11.3). Cloquet's node is known to be a poor predictor of pelvic spread. Pelvic LN disease was present in 50 per cent patients, but only 7 per cent had a pathology-positive Cloquet's node. CONCLUSION: Additional CT radiological characteristics, especially ECS and RM, may improve diagnostic accuracy and aid clinical decisions regarding the need for inguinal or ilioinguinal dissection.

Uterotonic drug usage in Canada: a snapshot of the practice in obstetric units of university-affiliated hospitals.

OBJECTIVE: The objective of this study was to determine the pattern of uterotonic drug usage in obstetric units of university-affiliated hospitals in Canada. METHODS: This was a prospective observational study conducted in the form of an electronic survey. The target group consisted of chiefs or directors of Obstetrics and Anaesthesia at university-affiliated hospitals across Canada. The survey was sent out between November 2016 and January 2017, using the program 'SurveyMonkey'. Data on institutional obstetric practices and usage of uterotonic agents were collected. RESULTS: The survey was sent to 92 obstetricians and anesthesiologists from 46 institutions, of which 33 clinicians from 24 institutions responded. About 65% of clinicians were unaware of the rate of postpartum hemorrhage in their institution. The first-line agent for vaginal deliveries was reported as oxytocin by 94% and carbetocin by 6% of physicians. For women at low-risk for postpartum hemorrhage when undergoing cesarean deliveries (CD), 66% reported oxytocin as the first-line uterotonic, while 34% reported carbetocin. For CDs at high-risk of postpartum hemorrhage, 60% of physicians reported oxytocin and 40% reported using carbetocin initially. The use of second-line uterotonics was also variable. The choice of uterotonic was mainly based on perceived efficacy and Society of Obstetricians and Gynaecologists of Canada guidelines. CONCLUSION: There is a lack of a unified approach to the use of uterotonic drugs for postpartum hemorrhage management in Canada. To improve the management of postpartum hemorrhage due to uterine atony, an evidence-based approach to usage and consensus between obstetricians and anesthesiologists is warranted.

Assessing the incidence of peripartum subclinical myocardial ischemia using the troponin T assay: an observational pilot study.

BACKGROUND: Cardiac disease is the leading cause of maternal death. Non-fatal ischemic events may go unnoted during the time of delivery. The aim of this study was to assess the incidence of subclinical myocardial ischemia amongst parturients, as evidenced by a raised troponin assay in the postpartum period. METHODS: We undertook a prospective observational pilot study in a tertiary obstetric hospital with over 7000 deliveries a year. Targeted sampling was used to enter subjects in pre-defined high- or low-risk groups for myocardial strain, according to their clinical history and a brief questionnaire. Troponin T levels of 140 women were assessed between 8 and 24h postpartum. RESULTS: Ninety-one women considered to be at high risk and 49 at low risk women for myocardial strain were enrolled. The overall mean (±SD) serum troponin T level at 24h postpartum was 8.7±19.7ng/L (normal range <14ng/L). The incidence of a positive troponin result was 4.3% (95% CI 1.6, 9.1). Four patients (8.2%) of the low-risk group and two (2.2%) in the high-risk group had elevated troponin T assays. CONCLUSION: This study found that 4% of women had elevated postpartum troponin assays, within levels in the range suggestive of myocardial damage. However, we were unable to ascertain how to identify this group of women prospectively. At this time, we recommend a low threshold for investigation should be maintained.

Degradation of isolated deoxyribonucleic acid mediated by nitroso-chloramphenicol. Possible role in chloramphenicol-induced aplastic anemia.

Reduction of the nitro group of chloramphenicol (CAP) gives rise to more highly reactive intermediates which may in involved in the aplastic anemia associated with CAP use. One such intermediate, nitroso-chloramphenicol (NO-CAP), has been found to be a potent agent for mediating degradation of isolated DNA. In a reaction mixture containing 100 microM NO-CAP, 100 microM CuCl2, and 5 mM NADH, 7 micrograms of Escherichia coli [3H]DNA was completely degraded to acid-soluble fragments in 30 min. Damage to DNA was in the form of single-stranded scissions. The requirement for copper was specific, and copper chelating reagents blocked the degradation. The need for a reducing agent could be met equally well by NADH or NADPH, but not by sulfhydryl reagents such as glutathione, dithiothreitol and 2-mercaptoethanol. Oxygen was also necessary for the NO-CAP mediated DNA damage, with reduced forms of oxygen participating in the reaction. A role for H2O2 was indicated by the inhibition of the degradation seen when catalase was included in the mixture. Hydroxyl radicals are known to be produced in the reaction of H2O2 with certain transition metals. Scavangers of hydroxyl radicals also inhibited strand-scission, suggesting that the radicals may be the primary agents in DNA degradation. The importance of the nitroso moiety of NO-CAP was evidenced by the lack of DNA damage seen when NO-CAP was replaced by CAP under the conditions tested.

The benzylthio-pyrimidine U-31,355, a potent inhibitor of HIV-1 reverse transcriptase.

U-31,355, or 4-amino-2-(benzylthio)-6-chloropyrimidine is an inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and possesses anti-HIV activity in HIV-1-infected lymphocytes grown in tissue culture. The compound acts as a specific inhibitor of the RNA-directed DNA polymerase function of HIV-1RT and does not impair the functions of the DNA-catalyzed DNA polymerase or the Rnase H of the enzyme. Kinetic studies were carried out to elucidate the mechanism of RT inhibition by U-31,355. The data were analyzed using Briggs-Haldane kinetics, assuming that the reaction is ordered in that the template:primer binds to the enzyme first, followed by the addition of dNTP, and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived that allows the calculation of all the essential forward and backward rate constants for the reactions occurring between the enzyme, its substrates, and the inhibitor. The results obtained indicate that U-31,355 acts as a mixed inhibitor with respect to the template:primer and dNTP binding sites associated with the RNA-directed DNA polymerase domain of the enzyme. The inhibitor possessed a significantly higher binding affinity for the enzyme-substrate complexes, than for the free enzyme and consequently did not directly affect the functions of the substrate binding sites. Therefore, U-31,355 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either inhibition of the phosphoester bond formation or translocation of the enzyme relative to its template:primer following the formation of the ester bond. Moreover, the potency of U-31,355 depends on the base composition of the template:primer in that the inhibitor showed a much higher binding affinity for the enzyme-poly (rC):(dG)10 complexes than for the poly (rA):(dT)10 complexes.

Novelty seeking as a predictor of treatment retention for heroin dependent cocaine users.

This study examined the relationship between novelty seeking between treatment retention and among heroin dependent cocaine users. Participants were treated with buprenorphine maintenance and contingency management. The Tridimensional Personality Questionnaire's (TPQ) Novelty Seeking scale was administered to 68 participants prior to buprenorphine induction. Demographics, mood and anxiety disorders, antisocial personality disorder, and substance use were also assessed. Variables with significant relationships with overall retention were entered into a logistic regression analysis. In addition, using a survival analysis, all variables with significant relationships with time to drop-out were entered into a multivariate proportional hazards regression with time dependent covariates. Results demonstrated that although high novelty seekers, in comparison to low novelty seekers, were more likely to drop-out by the end of treatment, they had higher retention rates during the early phases of treatment. It is suggested that buprenorphine and contingency management were viewed by participants as novel treatment components and thus facilitated high novelty seekers' success early in treatment. If replicated, results suggest that inclusion of novel treatment components might facilitate retention among this at-risk group.

Impulsivity and voucher versus money preference in polydrug-dependent participants enrolled in a contingency-management-based substance abuse treatment program.

Thirty-four polydrug-dependent participants enrolled in a voucher-based substance abuse treatment program were given choices between hypothetical amounts of money and hypothetical amounts of vouchers, which are traded for goods and services, to determine their preferences for the two payment modalities. It was hypothesized that the majority of participants would prefer money to voucher because under the circumstances of the treatment program, the delay associated with money exchange is shorter than the delay associated with voucher exchange. It was further hypothesized that those participants who selected money over voucher also would have greater levels of impulsivity as assessed by the Barratt Impulsiveness Rating Scale (BIS) (Barratt, 1965). The results show large individual differences in money/voucher preference with approximately half of the participants preferring money to voucher when the two amounts are equivalent. In addition, as the magnitude of the money/voucher comparisons increased from 0.50 dollars to 32.00 dollars, the percentage of participants that preferred money increased. No correlations were found between money/voucher preference and impulsivity scores.

Contingency management for accurate predictions of urinalysis test results and lack of correspondence with self-reported drug use among polydrug abusers.

Contingency management procedures have proven effective in the treatment of drug-dependent patients. These procedures, however, often require frequent urine testing, which is too costly for community treatment programs. To make urine-testing procedures more cost effective, the feasibility of reinforcing accurate predictions of urine drug screen (UDS) results was evaluated. Participants made extremely accurate UDS predictions, particularly when they made drug-positive predictions, regardless of whether predictions were reinforced. However, self-reports of recent drug use had poor correspondence with predictions of UDS results. Results suggested that if programs only tested samples predicted to be drug free, considerable cost savings could be incurred. Further research is needed to determine if validity would be enhanced by using a proportion of costs saved to provide nominal reinforcement when samples were verified to be drug free.