Clinical risk management in obstetrics

PURPOSE OF REVIEW: Over recent years there has been a growing appreciation that a small but significant proportion of patients experience (sometimes serious) adverse events in the hands of health care workers. Although research in this area is very much in its infancy there has been an increasing move towards applying principles of risk management from industry to health care organizations. With the particularly disastrous and costly nature of adverse outcomes in obstetrics it is appropriate to review clinical risk management issues in maternity. RECENT FINDINGS: This review explores the appropriateness of applying lessons learned in industry to maternity. The classification of errors into individual and latent, or organizational, is examined. Furthermore, the way in which these errors can be identified and subsequently analysed, with examples from maternity units in the UK and USA, is discussed. The importance of an educational and supportive environment, rather than a blame culture, for both reporting of incidents and learning from adverse outcomes is emphasized. SUMMARY: Improvement in patient experience of health care rests not just with improved treatments, but also with a reduction in the adverse events which occur in health care institutions. The principles by which risk can be identified prospectively and retrospectively, and the mechanisms for both local risk management and regional/national reporting and learning are considered.     

The efficacy of supplemental magnesium in reducing atrial fibrillation after coronary artery bypass grafting

BACKGROUND: Atrial fibrillation after coronary artery bypass is reported from 17% to 53%. Hypomagnesemia after this surgery is considered a contributing factor. METHODS: Two hundred-two coronary bypass patients were randomized to magnesium (n = 105) or placebo (n = 97). The experimental group received 80-mg magnesium sulfate per kilogram ideal weight in 100 mL dextrose 5% water 30 minutes preoperatively. Postoperatively, patients received 8-mg magnesium sulfate per kilogram ideal weight intravenous per hour more than 48 hours. The control group received dextrose 5% water at these intervals. RESULTS: After the first bolus serum magnesium was experimental 4.75 mg/dL versus control 1.91 mg/dL, p less than 0.001, and remained different until postoperative day 4 (experimental 2.33 mg/dL vs control 2.26 mg/dL, p = 0.24). Atrial appendage and strap muscle were analyzed after the first bolus and after revascularization. There were no differences between groups in tissue magnesium or calcium. Urinary magnesium was elevated in the experimental (experimental 324.5 mg/24 hours, vs control 45.1 mg/24 hours, p = 0.01). Calcium excretion was higher (experimental 370 mg/24 hours vs control 186 mg/24 hours, p < 0.001) and was associated with lower serum calcium. Serum calcium was higher in the control through the fourth postoperative day. The incidence of atrial fibrillation was experimental 32 of 105 (30.5%) versus control 41 of 97 (42.3%) p = 0.08. Atrial fibrillation was different on the first postoperative day (experimental 3/105, 2.9% vs control 9/97, 9.3%), p = 0.05. CONCLUSIONS: Overall prophylactic magnesium supplementation does not significantly reduce atrial and ventricular arrhythmias. The only significant benefit of magnesium supplementation was on the first postoperative day.     

Alterations in mineral composition observed in osteoarthritic joints of cynomolgus monkeys

Osteoarthritis (OA) is a prevalent joint disease that affects more than 40 million Americans and is characterized by degeneration of the articular cartilage and thickening of the underlying subchondral bone. Although subchondral bone thickening has been implicated in articular cartilage degeneration, very little is known about the composition of subchondral bone in OA. In the present study, infrared microspectroscopy (IRMS) was used to determine the chemical composition of the calcified cartilage-subchondral bone plate in a monkey model of OA. Specifically, the levels of mineralization (mineral/protein ratio), carbonate accumulation (carbonate/protein ratio), crystallinity, and collagen structure were determined as a function of animal age and OA severity. OA severity was assessed using a grading scheme that included scores or measurements for several histomorphometric parameters including articular cartilage fibrillation or clefting, subchondral bone thickness, and numbers of tidemarks and chondrocyte clones. Individual scores and measurements were summarized using principal components (factor) analysis. Results demonstrated that the level of mineralization and carbonate content increased as a function of animal age. In addition, bone mineralization level increased as subchondral bone thickness increased. Dramatic increases in the mineralization level and carbonate accumulation were also observed as a function of the number of tidemarks. The presence of multiple tidemarks indicates the occurrence of one or more additional phases of cartilage calcification, suggesting that the observed compositional changes are due to cartilage mineralization. Our results support a reactivation of endochondral ossification that occurs with age, which is more pronounced in OA. No relationships were observed between mineral crystallinity and collagen cross-linking as a function of age or OA severity. In summary, compositional analysis of the mineralized plate beneath the articular cartilage in OA is characterized by thickened, overmineralized calcified cartilage or subchondral bone, which likely puts added mechanical stress on the joint, contributing to the progression of OA.     

Reductions in functional balance, coordination, and mobility measures among patients with stable chronic obstructive pulmonary disease

PURPOSE: To compare measures of balance, coordination, and mobility between patients with chronic obstructive pulmonary disease (COPD) and healthy control subjects, and to determine whether differences in these measures are associated with measures of disease severity. METHODS: The subjects were divided into three groups: 15 patients with COPD who required the use of supplemental oxygen (WO), 15 patients with COPD who did not require the use of supplemental oxygen (NO), and 21 healthy control subjects (CO). The subjects performed spirometry and several measures of balance, coordination, and mobility including the Community Balance and Mobility Scale, the timed up and go test, the fast-gait speed test, posturography, and both a finger-to-nose test and a toe-tapping coordination test. Significance was set at an alpha less than 0.05. RESULTS: When control was used for age, significant differences were found between the WO group and the CO group for the finger-to-nose test, and for both the sway index and peak sway index for the eyes open, moving-platform test. Differences were found among all three groups for the Community Balance and Mobility Scale overall score. The scores for the WO group were significantly worse than for the NO group on the timed up and go and the fast-gait speed tests. Moderate correlation was found among all of the measures, demonstrating significant differences in forced-expiratory volume in 1 second (FEV1), peak expiratory flow, and forced-expiratory volume. When controls were used for both age and FEV1, between-group differences disappeared. CONCLUSIONS: Patients with COPD exhibit deficiencies in functional balance, coordination, and mobility tasks associated with disease severity or differences in activity levels, but not in the requirement for supplemental oxygen.     

Molecular analysis of pediatric brain tumors

The identification of molecular genetic abnormalities in specific types of pediatric brain tumors is beginning to play a role in the stratification of patients into treatment groups. The finding of an INI1 alteration in an atypical teratoid/ rhabdoid tumor or malignant neoplasm with overlapping histologic features will be required for entry onto diseasespecific protocols within the Children’s Oncology Group. Refinement in the classification of medulloblastoma and malignant glioma patients will likely depend on the genetic and signaling pathways that characterize these tumors. Advances in this area will depend on the ability to identify new disease genes, validate prognostic markers, and develop biologically based therapeutic strategies to tailor treatment.     

Evolving applications in the use of bone-anchored hearing aids

The bone-anchored hearing aid (BAHA) is an effective means of intervention, its use being well documented in persons with chronic conductive pathology and congenital aural anomalies. This article describes the standard guidelines (both auditory and extraauditory aspects) for patient selection and expands the criteria to include bilateral BAHA implantation, unilateral conductive hearing loss, and unilateral profound sensorineural hearing loss. The BAHA's development, design features, and patient outcomes are also reviewed. Suggestions are presented for fitting, counseling, and following BAHA users.     

Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases

The identification of 8-ethyl-2-phenylamino-8H-pyrido[2, 3-d]pyrimidin-7-one (1) as an inhibitor of Cdk4 led to the initiation of a program to evaluate related pyrido[2, 3-d]pyrimidin-7-ones for inhibition of cyclin-dependent kinases (Cdks). Analysis of more than 60 analogues has identified some clear SAR trends that may be exploited in the design of more potent Cdk inhibitors. The most potent Cdk4 inhibitors reported in this study inhibit Cdk4 with IC(50) = 0.004 microM ([ATP] = 25 microM). X-ray crystallographic analysis of representative compounds bound to the related kinase, Cdk2, reveals that they occupy the ATP binding site. Modest selectivity between Cdks is exhibited by some compounds, and Cdk4-selective inhibitors block pRb(+) cells in the G(1)-phase of the cell division cycle.     

Phosphorylation of the cytoplasmic domain of the MUC1 mucin correlates with changes in cell-cell adhesion

The MUC1 epithelial mucin is expressed by glandular epithelial cells and is often highly expressed and associated with poor prognosis in adenocarcinomas. Tyrosine phosphorylation of the highly conserved cytoplasmic tail of MUC1 (MUC1-CT) has been demonstrated in MUC1 transfected cells and in one breast cancer cell line. In addition, associations between MUC1 and secondary signalling molecules have been demonstrated in breast cancer cell lines. MUC1 clearly plays a role in intracellular signalling, since we were able to demonstrate tyrosine phosphorylation of the MUC1-CT in breast and ovarian cancer cell lines and in primary cultures of serous ovarian cancers. We were unable to modulate MUC1-CT phosphorylation using conditioned media from cell lines showing the highest levels of signalling. However, in several breast and ovarian cancer cell lines, we clearly showed the highest levels of MUC1-CT tyrosine phosphorylation occurred during recolonisation of culture dishes or in low-density adherent cultures. We now hypothesise that phosphorylation changes may reflect either involvement of MUC1 in cell motility or a redistribution of MUC1 in the membrane during the course of cell-cell adhesion.