Evaluation of StrepBSelect Chromogenic Medium and the Fast-Track Diagnostics Group B Streptococcus (GBS) Real-Time PCR Assay Compared to Routine Culture for Detection of GBS during Antepartum Screening.

Life-threatening infection in neonates due to group B Streptococcus (GBS) is preventable by screening of near-term pregnant women and treatment at delivery. A total of 295 vaginal-rectal swabs were collected from women attending antepartum clinics in Calgary, Alberta, Canada. GBS colonization was detected by the standard culture method (Strep B Carrot Broth subcultured to blood agar with a neomycin disk) and compared to recovery with Strep Group B Broth (Dalynn Biologicals) subcultured to StrepBSelect chromogenic medium (CM; Bio-Rad Laboratories) and the Fast-Track Diagnostics GBS real-time PCR (quantitative PCR [qPCR]) assay (Phoenix Airmid Biomedical Corp.) performed with broth-enriched samples and the Abbott m2000sp/m2000rt system. A total of 62/295 (21%) women were colonized with GBS; 58 (19.7%) cases were detected by standard culture, while CM and qPCR each found 61 (20.7%) cases. The qPCR and CM were similar in performance, with sensitivities, specificities, and positive and negative predictive values of 98.4 and 98.4%, 99.6 and 99.6%, 98.4 and 98.4%, and 99.6 and 99.6%, respectively, compared to routine culture. Both qPCR and CM would allow more rapid reporting of routine GBS screening results than standard culture. Although the cost per test was similar for standard culture and CM, the routine use of qPCR would cost approximately four times as much as culture-based detection. Laboratories worldwide should consider implementing one of the newer methods for primary GBS testing, depending on the cost limitations of different health care jurisdictions.

Gastrointestinal complications after cardiac surgery: 10-year experience of a single Australian centre.

BACKGROUND: Gastrointestinal (GI) complications after cardiac surgery are uncommon, but are associated with high morbidity and mortality as well as significant hospital resource utilization. METHODS: We analysed a prospectively collected database containing all adult cardiac surgery procedures performed from July 2001 to March 2011 at Monash Medical Centre and Jessie McPherson Private Hospital. Patients with post-operative GI complications were compared to patients without GI complications who were operated in the same period. RESULTS: The incidence of GI complications was 1.1% (61 out of 5382 patients) with an overall 30-day mortality of 33% (versus 3% in the non-GI complication group). The most common complications were GI bleeding, gastroenteritis and bowel ischaemia. Patients who had GI complications were significantly older, had higher incidence of renal impairment, chronic lung disease and anticoagulation therapy and were more likely to be in cardiogenic shock. Emergency procedures, combined coronary artery bypass grafting and valve surgery and aortic dissection cases were more common in the GI complication group. The GI complication group also had higher incidence of return to theatre, renal failure, stroke, septicaemia and multi-organ failure. CONCLUSIONS: GI complications after cardiac surgery remain an uncommon but dreadful complication associated with high mortality. Our findings should prompt a high degree of clinical vigilance in order to make an early diagnosis especially in high risk patients. Further studies aiming to identify independent predictors for GI complications after cardiac surgery are warranted.

Medical educators' perspectives of teaching physical examinations using ultrasonography at the undergraduate level.

BACKGROUND: Ultrasonography is increasingly used for teaching physical examination in medical schools. This study seeks the opinions of educators as to which physical examinations would be most enhanced by the addition of ultrasonography. We also asked when ultrasound-aided physical examination teaching could have deleterious effects if used outside its intended scope. METHODS: All of the educators from the University of Calgary Master Teacher Program were invited to complete a 22-item paper-based survey. Survey items were generated independently by two investigators, with input from an expert panel (n = 5). RESULTS: Of the 36 educators, 27 (75%) completed the survey. Examinations identified to be potentially most useful included: measuring the size of the abdominal aorta, identifying the presence/absence of ascites, identifying the presence/absence of pleural effusions, and measuring the size of the bladder. Examinations thought to be potentially most harmful included: identifying the presence/absence of intrauterine pregnancy, measuring the size of the abdominal aorta, and identifying the presence/absence of pericardial effusion. CONCLUSIONS: Examinations that are potentially the most useful may also be potentially the most harmful. When initiating an ultrasound curriculum for physical examinations, educators should weigh the risks and benefits of examinations chosen.

Emotion, cognitive load and learning outcomes during simulation training.

CONTEXT: Simulation training has emerged as an effective way to complement clinical training of medical students. Yet outcomes from simulation training must be considered suboptimal when 25-30% of students fail to recognise a cardiac murmur on which they were trained 1 hour previously. There are several possible explanations for failure to improve following simulation training, which include the impact of heightened emotions on learning and cognitive overload caused by interactivity with high-fidelity simulators. This study was conducted to assess emotion during simulation training and to explore the relationships between emotion and cognitive load, and diagnostic performance. METHODS: We trained 84 Year 1 medical students on a scenario of chest pain caused by symptomatic aortic stenosis. After training, students were asked to rate their emotional state and cognitive load. We then provided training on a dyspnoea scenario before asking participants to diagnose the murmur in which they had been trained (aortic stenosis) and a novel murmur (mitral regurgitation). We used factor analysis to identify the principal components of emotion, and then studied the associations between these components of emotion and cognitive load and diagnostic performance. RESULTS: We identified two principal components of emotion, which we felt represented invigoration and tranquillity. Both of these were associated with cognitive load with adjusted regression coefficients of 0.63 (95% confidence interval [CI] 0.28-0.99; p = 0.001) and - 0.44 (95% CI - 0.77 to - 0.10; p = 0.009), respectively. We found a significant negative association between cognitive load and the odds of subsequently identifying the trained murmur (odds ratio 0.27, 95% CI 0.11-0.67; p = 0.004). CONCLUSIONS: We found that increased invigoration and reduced tranquillity during simulation training were associated with increased cognitive load, and that the likelihood of correctly identifying a trained murmur declined with increasing cognitive load. Further studies are needed to evaluate the impact on performance of strategies to alter emotion and cognitive load during simulation training.

Evaluation of the Xpert® group B streptococcus real-time polymerase chain reaction assay compared to StrepB Carrot Broth™ for the rapid intrapartum detection of group B streptococcus colonization.

Xpert group B streptococcus (GBS) was compared to StrepB Carrot Broth™ (SCB) for the detection of intrapartum GBS colonization by dually collecting vaginal/rectal swabs from 231 women. Xpert GBS detected all of the cases (45, 19.5%), but 4 were missed by SCB. A rapid Xpert GBS service for women in labor would increase costs by ∼$55.000 per annum in our region.

Rapid automation of a cell-based assay using a modular approach: case study of a flow-based Varicella Zoster Virus infectivity assay.

Vaccine manufacturing requires constant analytical monitoring to ensure reliable quality and a consistent safety profile of the final product. Concentration and bioactivity of active components of the vaccine are key attributes routinely evaluated throughout the manufacturing cycle and for product release and dosage. In the case of live attenuated virus vaccines, bioactivity is traditionally measured in vitro by infection of susceptible cells with the vaccine followed by quantification of virus replication, cytopathology or expression of viral markers. These assays are typically multi-day procedures that require trained technicians and constant attention. Considering the need for high volumes of testing, automation and streamlining of these assays is highly desirable. In this study, the automation and streamlining of a complex infectivity assay for Varicella Zoster Virus (VZV) containing test articles is presented. The automation procedure was completed using existing liquid handling infrastructure in a modular fashion, limiting custom-designed elements to a minimum to facilitate transposition. In addition, cellular senescence data provided an optimal population doubling range for long term, reliable assay operation at high throughput. The results presented in this study demonstrate a successful automation paradigm resulting in an eightfold increase in throughput while maintaining assay performance characteristics comparable to the original assay.

Evaluation of StrepB carrot broth versus Lim broth for detection of group B Streptococcus colonization status of near-term pregnant women.

The performance of StrepB Carrot Broth (SCB) versus group B Lim broth (LIM) for detection of group B streptococcus (GBS) colonization status in near-term pregnant women (35 to 37 weeks of gestation) was evaluated. Dually collected vaginal/rectal swabs from 279 women enrolled from a single large maternity clinic were analyzed. Fifty (18%) women were colonized by GBS according to both methods. SCB had excellent diagnostic performance compared to LIM, with sensitivity, specificity, positive predictive value, and negative predictive value of 92%, 100%, 100%, and 98.3%, respectively. Improved diagnostic efficiency due to direct reporting of GBS cases based on an orange color change in the SCB decreased overall labor and material costs.

Flexible low-intensity combination chemotherapy for elderly patients with acute myeloid leukaemia: a multicentre, phase II study.

OBJECTIVE: To evaluate the efficacy of a flexible low-intensity combination chemotherapy (FLICC) protocol in a multicentre, phase II study of elderly patients with acute myeloid leukaemia (AML). METHOD: Twenty-five patients aged 61-78 years (median 70 years) with de novo (n = 17) or secondary (n = 8) AML (cytogenetic risk: favourable 2, intermediate 18, adverse 2, unknown 3) from eight Australian centres were enrolled. Treatment comprised mitoxantrone 6 mg/m(2) intravenously daily for 3 days, cytarabine 10mg/m(2) subcutaneously every 12 hours for 7-14 days and etoposide 100mg orally for 7-14 days. RESULTS: The treatment was generally well tolerated, and 13 patients (52%) achieved a complete remission (CR). One patient achieved a partial remission but died on day 28 due to pneumonia. Five patients (20%) had no response, whilst six (24%) died on or before day 30 and so were not evaluable. The median overall survival (OS) was 6.5 months, and the median remission duration was 7.7 months. Estimated 1-year survival was 32%, but patients achieving CR had an estimated 1-year survival of 64%, whereas none in the non-CR group survived to 1 year. Two of the CR patients have survived beyond 2 years. OS was significantly shorter in the adverse cytogenetic risk group of patients compared with the favourable- and intermediate-risk groups, with the rates of death relative to the adverse group being 0.02 and 0.08 in the favourable- and intermediate-risk groups, respectively. There was no significant association between CR rate and pre-existing myelodysplasia or the presence of multilineage dysplasia. The median durations of significant neutropenia (<0.5 x 10(9)/L) and thrombocytopenia (<20 x10(9)/L) with the first course of treatment in the 19 evaluable patients were 19 days (range 12-26) and 11 days (range 1-25), respectively. The median duration of stay in the hospital was 27 days (range 14-42). These values were much shorter for the second course of treatment: 6 days, 5 days and 15 days, respectively. CONCLUSION: The findings of this multicentre, phase II study validate the previously reported single-institution experience with the FLICC protocol in elderly patients with AML. The clinical outcome with this protocol is comparable to those reported with more aggressive anti-leukaemia protocols.

Molecular mechanisms of regulation of fast-inactivating voltage-dependent transient outward K+ current in mouse heart by cell volume changes.

The K(v)4.2/4.3 channels are the primary subunits that contribute to the fast-inactivating, voltage-dependent transient outward K(+) current (I(to,fast)) in the heart. I(to,fast) is the critical determinant of the early repolarization of the cardiac action potential and plays an important role in the adaptive remodelling of cardiac myocytes, which usually causes cell volume changes, during myocardial ischaemia, hypertrophy and heart failure. It is not known, however, whether I(to,fast) is regulated by cell volume changes. In this study we investigated the molecular mechanism for cell volume regulation of I(to,fast) in native mouse left ventricular myocytes. Hyposmotic cell swelling caused a marked increase in densities of the peak I(to,fast) and a significant shortening in phase 1 repolarization of the action potential duration. The voltage-dependent gating properties of I(to,fast) were, however, not altered by changes in cell volume. In the presence of either protein kinase C (PKC) activator (12,13-dibutyrate) or phosphatase inhibitors (calyculin A and okadaic acid), hyposmotic cell swelling failed to further up-regulate I(to,fast). When expressed in NIH/3T3 cells, both K(v)4.2 and K(v)4.3 channels were also strongly regulated by cell volume in the same voltage-independent but PKC- and phosphatase-dependent manner as seen in I(to,fast) in the native cardiac myocytes. We conclude that K(v)4.2/4.3 channels in the heart are regulated by cell volume through a phosphorylation/dephosphorylation pathway mediated by PKC and serine/threonine phosphatase(s). These findings suggest a novel role of K(v)4.2/4.3 channels in the adaptive electrical and structural remodelling of cardiac myocytes in response to myocardial hypertrophy, ischaemia and reperfusion.

A randomized trial of high-versus conventional-dose cytarabine in consolidation chemotherapy for adult de novo acute myeloid leukemia in first remission after induction therapy containing high-dose cytarabine.

The value of administering sequential courses of chemotherapy containing high-dose cytarabine in both induction and consolidation therapy for acute myeloid leukemia (AML) has not been assessed in a prospective randomized trial. Two hundred ninety-two AML patients aged 15 to 60 years were enrolled in the Australasian Leukaemia and Lymphoma Group (ALLG) AML trial number 7 (M7) protocol to evaluate this question. All received induction therapy with the ICE protocol (idarubicin 9 mg/m2 x 3; cytarabine 3 g/m2 twice a day on days 1, 3, 5, 7; etoposide 75 mg/m2 x 7). Complete remission was achieved in 234 (80%) patients. Two hundred two patients in remission were then randomized to either a further identical cycle of ICE or 2 attenuated courses (cytarabine 100 mg/m2 daily x 5, idarubicin x 2, etoposide x 5 [IcE]). ICE consolidation therapy was more toxic than IcE, however, the treatment-related death rate was not significantly different. There was no difference between the 2 consolidation arms for relapse-free survival at 3 years (49% for ICE vs 46% for IcE; P = .66), survival following randomization (61% vs 62%; P = .91), or the cumulative incidence of relapse (43% vs 51%; P = .31), and there was no difference within cytogenetic risk groups. Intensive induction chemotherapy incorporating high-dose cytarabine results in high complete remission rates, but further intensive consolidation treatment does not appear to confer additional benefit.

A comparison of pregnant women presenting for alcohol and other drug treatment by CPS status.

OBJECTIVE: The purpose of this study was to describe the demographic, substance use, and treatment variables of alcohol and other drug (AOD) treatment seeking pregnant women. This study also compared women on these variables based on Child Protective Service (CPS) status. METHOD: Secondary data of all pregnant women with at least one child entering all publicly funded AOD treatment programs (N=678), in a southwest county, over a 3-year period were analyzed to examine the differences between pregnant women also involved with CPS and those not involved with CPS. RESULTS: Pregnant women reporting CPS involvement were similar to non-CPS women on demographic variables but differed on drug use and treatment variables. CPS women were more likely to report marijuana use as their primary problem drug, be mandated to treatment, attend day treatment and be released from treatment unsatisfactorily compared to the non-CPS pregnant women. Those without CPS involvement were more likely to report cocaine or crack as their primary drug, attend outpatient treatment and be found to have a satisfactory release from treatment compared to those with CPS involvement. Results from the multiple logistic regression analysis found that the significant predictors of CPS involvement were mandated status and unsatisfactory treatment release. CONCLUSIONS: Differences in treatment outcomes may be based on AOD agencies' difficulty in working with mandated clients and/or with the multiple demands placed by CPS on clients as part of their treatment plans. Further research is needed to determine reasons for CPS clients' high failure rates in AOD treatment.