Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension.

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

Evaluating the performance of National Comprehensive Cancer Network (NCCN) breast and ovarian genetic/familial high risk assessment referral criteria for breast cancer women in an Asian surgical breast clinic.

BACKGROUND: Globally, resources for genomic services vary. Current National Comprehensive Cancer Network (NCCN) breast and ovarian genetic/familial high risk assessment criteria for further genetic risk evaluation are useful, but lack specificity for reliably excluding patients with low a priori risk. This may result in patient overload in lesser-equipped genetics clinics. Since we use Manchester and the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) risk assessment models in our genetics clinic to determine whether genetic testing is warranted, we chose Manchester and BOADICEA as the reference standard to compare how the NCCN breast and ovarian genetic/familial high risk assessment criteria for further genetic risk evaluation performs against these two risk assessment models in referring breast cancer patients for genetic evaluation. METHODS: Breast cancer patients diagnosed from 2009-2011 were assessed using the NCCN criteria, Manchester and BOADICEA. Logistic regression and receiver operating characteristic (ROC) analysis were used to compare the NCCN criteria versus the Manchester and BOADICEA scoring systems in identifying high-risk patients. RESULTS: A total of 666 patients were included in the study. Percentages of high-risk patients resulting from Manchester and BOADICEA were 1.80% and 2.55%, respectively. Among the NCCN criteria, breast cancer and ≥1 close relatives with breast cancer at ≤50 years of age correlated best with Manchester and/or BOADICEA (c-statistic =0.831) with a false negative rate of 1.0%. CONCLUSIONS: Breast cancer at any age and ≥1 close relative with breast cancer at ≤50 years of age exhibited the highest correlation with Manchester and/or BOADICEA, promising greater specificity compared to the other NCCN criteria for segregating high risk, Asian breast cancer patients for referral to a genetics clinic, nevertheless recognizing the inherent limitations of the scoring systems.

What factors influence midwives' decision to perform or avoid episiotomies? A focus group study.

OBJECTIVE: to explore midwives' reasons for performing or avoiding episiotomies and motivation to change episiotomy practice in a large tertiary maternity hospital. DESIGN: using purposive sampling, three focus groups were conducted to achieve theme saturation. Open-ended questions elicited personal reasons for performing or avoiding episiotomy, information sources, and opinions about past and future practice trends. Sessions were audiotaped, and transcripts independently examined by three researchers who coded for themes. An iterative process was used to achieve consensus. Grounded theory was used to interpret data and to derive a theoretical framework for understanding the reasoning that influences episiotomy practice. SETTING: a high volume delivery unit in Singapore. PARTICIPANTS: 20 of 79 licensed midwives, aged 28-70, who performed independent deliveries at the delivery unit. FINDINGS: participants recognised maternal, fetal and other factors affecting their own decision to perform episiotomies. Patient request, better healing, midwife's reputation and job satisfaction were cited as main reasons to avoid episiotomy. Key sources informing practice were past training, delivery experience, anecdotal learning and lack of a protocol. There was no consensus on current trends in episiotomy practice. There was an absence of recognition of individual roles in reducing episiotomy rates. Clinicians were perceived as having both positive and negative influence. CONCLUSIONS: midwives' reasons for performing episiotomies were attributed to midwifery training, fear of doing harm and perceived clinician expectation, and were not consistent with current international practice guidelines. Reasons for avoiding episiotomies were associated with patient-centeredness and job satisfaction. Midwives agreed on the need to reduce episiotomy rates. IMPLICATIONS FOR PRACTICE: with reduction in episiotomy rates as a goal, a combination of guideline education, feedback, peer coaching and collaborative care with doctors may be needed to achieve desired outcomes. Views and experiences of midwives should also be incorporated into strategies to change episiotomy practice.

A 1-year pilot study of vagus nerve stimulation in treatment-resistant rapid-cycling bipolar disorder.

OBJECTIVE: Vagus nerve stimulation (VNS) appears to be an effective treatment option for patients with treatment-resistant unipolar and bipolar depression. The aim of the present study was to investigate the efficacy of VNS in a group of patients with treatment-resistant rapid-cycling bipolar disorder (RCBD) who were excluded from previous trials. METHOD: Nine outpatients with a DSM-IV-TR diagnosis of treatment-resistant RCBD were treated for 40 weeks with open-label VNS. The first patient was enrolled in June 2001, and the last patient completed the study in July 2005. Patients recorded their depression and mania mood symptoms on a daily basis throughout the study using the National Institute of Mental Health prospective life charting methodology and daily mood ratings. Patients were assessed every 2 weeks during the 2-month baseline period before device activation, every 2 weeks for the remaining 40 weeks of the study, and at the end of the study with the 24-item Hamilton Rating Scale for Depression (HAM-D-24), the 10-item Montgomery-Asberg Depression Rating Scale (MADRS), the Young Mania Rating Scale (YMRS), the Clinical Global Impressions (CGI) scale, the Global Assessment of Functioning (GAF) scale, and the 30-item Inventory of Depressive Symptomatology Self-Report (IDS-SR-30). Any adverse events or device complications were also recorded at each visit. The prospective life charts were analyzed by calculating the area under the curve. Statistical analysis was performed with a mixed-model repeated-measures regression analysis for repeated measures of the various rating scales. Significant p values were < or = .05. RESULTS: Over the 12-month study period, VNS was associated with a 38.1% mean improvement in overall illness as compared to baseline (p = .012), as well as significant reductions in symptoms as measured by the HAM-D-24 (p = .043), MADRS (p = .003), CGI (p = .013), and GAF (p < .001) rating scales. Common adverse events were voice alteration during stimulation and hoarseness. CONCLUSION: These data suggest that VNS may be an efficacious and well-tolerated treatment option for patients with treatment-resistant RCBD. Currently, no comparison is available in the literature. Larger randomized trials are needed to verify these findings.

A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia.

OBJECTIVE: Magnesium sulfate may prevent eclampsia by reducing cerebral vasoconstriction and ischemia. Nimodipine is a calcium-channel blocker with specific cerebral vasodilator activity. Our objective was to determine whether nimodipine is more effective than magnesium sulfate for seizure prophylaxis in women with severe preeclampsia. METHODS: We conducted an unblinded, multicenter trial in which 1650 women with severe preeclampsia were randomly assigned to receive either nimodipine (60 mg orally every 4 hours) or intravenous magnesium sulfate (given according to the institutional protocol) from enrollment until 24 hours post partum. High blood pressure was controlled with intravenous hydralazine as needed. The primary outcome measure was the development of eclampsia, as defined by a witnessed tonic-clonic seizure. RESULTS: Demographic and clinical characteristics were similar in the two groups. The women who received nimodipine were more likely to have a seizure than those who received magnesium sulfate (21 of 819 [2.6 percent] vs. 7 of 831 [0.8 percent], P=0.01). The adjusted risk ratio for eclampsia associated with nimodipine, as compared with magnesium sulfate, was 3.2 (95 percent confidence interval, 1.1 to 9.1). The antepartum seizure rates did not differ significantly between groups, but the nimodipine group had a higher rate of postpartum seizures (9 of 819 [1.1 percent] vs. 0 of 831, P=0.01). There were no significant differences in neonatal outcome between the two groups. More women in the magnesium sulfate group than in the nimodipine group needed hydralazine to control blood pressure (54.3 percent vs. 45.7 percent, P<0.001). CONCLUSIONS: Magnesium sulfate is more effective than nimodipine for prophylaxis against seizures in women with severe preeclampsia.