PAX fusion proteins deregulate gene networks controlling mitochondrial translation in pediatric rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (ARMS) patients harboring PAX3-FOXO1 and PAX7-FOXO1 fusion proteins exhibit a greater incidence of tumor relapse, metastasis, and poor survival outcome, thereby underscoring the urgent need to develop effective therapies to treat this subtype of childhood cancer. To uncover mechanisms that contribute to tumor initiation, we developed a novel muscle progenitor model and used epigenomic approaches to unravel genome re-wiring events mediated by PAX3/7 fusion proteins. Importantly, these regulatory mechanisms are conserved across established ARMS cell lines, primary tumors, and orthotopic-patient derived xenografts. Among the key targets of PAX3- and PAX7-fusion proteins, we identified a cohort of oncogenes, FGF receptors, and genes essential for mitochondrial metabolism and protein translation, which we successfully targeted in preclinical trials. Our data suggest an explanation for the relative paucity of recurring mutations in this tumor, provide a compelling list of actionable targets, and suggest promising new strategies to treat this tumor.

Public-Private Partnerships to Lower the Risk of Diabetes Among Black Women Using Cooperative Agreements: The National Diabetes Prevention Program and the Black Women's Health Imperative.

The National Diabetes Prevention Program (National DPP) is a partnership of public and private organizations working to build a nationwide delivery system for a lifestyle change program (LCP), which is proved to prevent or delay onset of type 2 diabetes in adults with prediabetes. Through this program, the Centers for Disease Control and Prevention (CDC) establishes partnerships with organizations to prevent or delay the onset of type 2 diabetes by using the evidence-based and audience-tailored LCP. The DP17-1705 cooperative agreement aims to expand the reach of the program in underserved areas and to populations currently underrepresented in the program relative to their risk. This article highlights a successful adaptation of the National DPP PreventT2 curriculum to address the needs of women who are Black funded by this cooperative agreement. The Change your Lifestyle, Change your Life (CYL2) program resulted from a partnership between CDC and the Black Women's Health Imperative. Successes and challenges associated with this program are highlighted. Lessons learned from these efforts can be used by practitioners to inform future type 2 diabetes prevention initiatives.

Enhancing the Adoption of Evidence-Based Health Marketing and Promotion Strategies in Local Communities: Building a Communication Dissemination and Support System for the National Diabetes Prevention Program.

The Centers for Disease Control and Prevention (CDC) created a health communication marketing and promotion support system (support system) to help 10 CDC-funded national organizations (recipients) grow enrollment of underserved populations in the National Diabetes Prevention Program. This article describes the creation of a successful support system to increase the use of effective marketing approaches and key messaging. The support system was developed using a systematic approach. It included a needs assessment, audience research, marketing strategy identification, expert panel review, materials development, and dissemination guidance. Hands-on, individualized, and group end-user training and technical assistance was also included. Recipients received culturally and linguistically tailored marketing materials to support their specific priority audiences, as well as corresponding training on recommended dissemination methods. In in-depth key-informant interviews, staff from six recipients reported increased knowledge of local communities and audiences, efficacy and skills to conduct media interviews, capacity to identify and train champions and influencers, and greater community partner investments. With marketing support, 90% of recipients reported increased enrollment, of which 40% exceeded self-set targets and another 40% doubled or tripled their enrollment numbers. These findings indicate that a customized strategic health communication marketing and promotion support system presents a significant opportunity to help recipients increase enrollment in evidence-based interventions. Practitioners disseminating evidence-based interventions may consider a support system to increase program uptake.

Maternal Asian ethnicity and obstetric intrapartum intervention: a retrospective cohort study.

BACKGROUND: Maternal ethnicity is a recognized risk factor for stillbirth, such that South Asian women have higher rates than their Caucasian counterparts. However, whether maternal ethnicity is a risk factor for intrapartum outcomes is less clear. The aim of this study is to explore associations between maternal country of birth, operative vaginal delivery and emergency cesarean section, and to identify possible mechanisms underlying any such associations. METHODS: We performed a retrospective cohort study of singleton term births among South Asian, South East/East Asian and Australian/New Zealand born women at an Australian tertiary hospital in 2009-2013. The association between maternal country of birth, operative vaginal birth and emergency cesarean was assessed using multivariate logistic regression. RESULTS: Of the 31,932 births, 54% (17,149) were to Australian/New Zealand-born women, 25% (7874) to South Asian, and 22% (6879) to South East/East Asian born women. Compared to Australian/New Zealand women, South Asian and South East/East Asian women had an increased rate of both operative vaginal birth (OR 1.43 [1.30-1.57] and 1.22 [1.11-1.35] respectively, p < 0.001 for both) and emergency cesarean section (OR 1.67 [1.53-1.82] and 1.16 [1.04-1.26] respectively, p < 0.001 and p = 0.007 respectively). While prolonged labor was the predominant reason for cesarean section among Australian/New Zealand and South East/East Asian women, fetal compromise accounted for the majority of operative births in South Asian women. CONCLUSION: South Asian and South East/East Asian women experience higher rates of both operative vaginal birth and cesarean section in comparison to Australian/New Zealand women, independent of other risk factors for intrapartum interventions.

Customised management of the third stage of labour.

BACKGROUND: Postpartum haemorrhage (PPH) rates are increasing worldwide. The rate is particularly high in women undergoing an induced or augmented labour. In response to this, we altered our hospital's protocol for the management of the third stage of labour to recommend Syntometrine, in preference to oxytocin alone, for women being induced or augmented. We set out to assess the impact of the protocol change on the PPH rate. MATERIALS AND METHODS: A random sample of 1200 women who had a singleton, term vaginal birth before and after the protocol change was taken. Exclusion criteria were then applied to match PPH risk status. Using a quasi-experimental study design, PPH rates were compared between women who had received oxytocin or Syntometrine for third stage management. RESULTS: Five hundred and forty-nine women received oxytocin prior to the protocol change and were compared with 333 women who received Syntometrine after protocol change. There was no difference in the PPH rate with respect to uterotonic used (P = 0.9). There was no evidence of an interaction between labour type, third stage uterotonic and PPH (P = 0.4). PPH rates were lowest for women who laboured spontaneously and received Syntometrine (19% oxytocin, 14% Syntometrine). The PPH rate was unchanged by uterotonic in women whose labour was augmented (34% for both). PPH was more common in women being induced who received Syntometrine (22% oxytocin, 27% Syntometrine). None of these differences were statistically significant. CONCLUSION: Compared to oxytocin, Syntometrine did not reduce the rate of PPH in women with augmented or induced labour. Other approaches to reducing PPH rates are required.

Optimal Interval between Ultrasound Scans for the Detection of Complications in Monochorionic Twins.

INTRODUCTION: Monochorionic-diamniotic (MCDA) twin pregnancies are high risk, due to twin-to-twin transfusion syndrome (TTTS), twin anaemia polycythaemia sequence (TAPS) and intrauterine growth restriction (IUGR). There is limited evidence to guide ultrasound surveillance protocols. Using a retrospective cohort, we aimed to provide insight into the optimal interval of ultrasound surveillance. METHODS: Retrospective cohort of women with MCDA pregnancies who received antenatal care at Monash Medical Centre (January 2011-October 2014). We reviewed all ultrasounds from ≥15 weeks' gestation and collected perinatal outcomes. RESULTS: A total of 162 women with MCDA pregnancies attended our care. Six women were excluded due to late referral. Of the remaining 156, 55% were uncomplicated. TTTS, TAPS, IUGR and fetal demise in utero occurred in 9%, 1%, 31% and 2%, respectively. Median interval between the last ultrasound and TTTS diagnosis was 3.1 weeks (IQR 0.8-5.8). There was a trend towards a longer interval for cases with advanced TTTS compared to early TTTS. Interval between ultrasound scans was longer in cases with unexplained fetal demise in utero and advanced TTTS than early TTTS [3.4 weeks (IQR 2.0-6.9) vs. 0.9 weeks (IQR 0.4-3.7); p < 0.05]. DISCUSSION: Our observations support current recommendations for fortnightly ultrasound surveillance in MCDA pregnancies from 16 weeks' gestation and suggest that longer intervals may be associated with poorer outcomes.

Obesity and pregnancy outcomes: Do the relationships differ by maternal region of birth? A retrospective cohort study.

BACKGROUND: We aimed to determine whether the association between obesity and a range of adverse maternal and perinatal outcomes differed in South Asian and Australian and New Zealand born women. METHODS: A retrospective cohort study of singleton births in South Asian (SA) and Australian/New Zealand (AUS/NZ) born women at an Australian hospital between 2009 and 2013. The interaction between maternal region of birth and obesity on a range of maternal and perinatal outcomes was assessed using multivariate logistic regression. RESULTS: Obesity was more strongly associated with gestational hypertension/Preeclampsia/HELLP and Gestational Diabetes Mellitus in AUS/NZ born women (p = 0.001 and p < 0.001, respectively for interaction) and was only associated with shoulder dystocia in SA born women (p = 0.006 for interaction). There was some evidence that obesity was more strongly related with admission to NICU/Special care nursery (SCN) (p = 0.06 for interaction) and any perinatal morbidity (p = 0.05 for interaction) in SA born women. CONCLUSIONS: Interventions targeted at reducing maternal obesity will have different impacts in SA compared to AUS/NZ born women.

Contemporary type 1 diabetes pregnancy outcomes: impact of obesity and glycaemic control.

OBJECTIVE: To compare contemporary pregnancy outcomes in women with and without type 1 diabetes, and to examine the effects of obesity and glycaemic control on these outcomes. DESIGN AND SETTING: Historical cohort study in a specialist diabetes and maternity network in Victoria. PARTICIPANTS: All singleton births (at least 20 weeks' gestation), 2010-2013, were analysed: 107 pregnancies to women with type 1 diabetes and 27 075 pregnancies to women without diabetes. Women with type 2 diabetes or gestational diabetes were excluded. METHODS: Data were extracted from the Birthing Outcomes System database; associations between type 1 diabetes and pregnancy outcomes were analysed by multivariable regression. MAIN OUTCOME MEASURES: Mode of birth; maternal and neonatal outcomes. RESULTS: The mean body mass index was higher for women with type 1 diabetes than for women without diabetes (mean, 27.3 kg/m(2) [SD, 5.0] v 25.7 kg/m(2) [SD, 5.9]; P = 0.01); the median gestation period for their babies was shorter (median, 37.3 weeks [IQR, 34.6-38.1] v 39.4 weeks [IQR, 38.4-40.4]; P < 0.001) and they were more likely to be large for gestational age (LGA) (adjusted odds ratio [aOR], 7.9; 95% CI, 5.3-11.8). Women with type 1 diabetes were more likely to have had labour induced (aOR, 3.0; 95% CI, 2.0-4.5), a caesarean delivery (aOR, 4.6; 95% CI, 3.1-7.0), or a pre-term birth (aOR, 6.7; 95% CI, 4.5-10.0); their babies were more likely to have shoulder dystocia (aOR, 8.2; 95% CI, 3.6-18.7), hypoglycaemia (aOR, 10.3; 95% CI, 6.8-15.6), jaundice (aOR, 5.1; 95% CI, 3.3-7.7), respiratory distress (aOR, 2.5; 95% CI, 1.4-4.4) or to suffer perinatal death (aOR, 4.3; 95% CI, 1.9-9.9). In women with type 1 diabetes, greater obesity was associated with increased odds for an LGA baby or congenital malformation, and increased HbA1c levels were associated with pre-term birth and perinatal death. CONCLUSION: Women with type 1 diabetes, even when managed in a specialist setting, still experience adverse obstetric and neonatal outcomes. Poor glycaemic control is not wholly responsible for adverse outcomes, reinforcing the importance of other risk factors, such as obesity and weight gain.

Nonstatin therapies for management of dyslipidemia: a review.

PURPOSE: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Recently published cholesterol treatment guidelines emphasize the use of statins as the preferred treatment strategy for both primary and secondary prevention of CVD. However, the optimal treatment strategy for patients who cannot tolerate statin therapy or those who need additional lipid-lowering therapy is unclear in light of recent evidence that demonstrates a lack of improved cardiovascular outcomes with combination therapy. The purpose of this review is to summarize and interpret evidence that evaluates nonstatin drug classes in reducing cardiovascular outcomes, to provide recommendations for use of nonstatin therapies in clinical practice, and to review emerging nonstatin therapies for management of dyslipidemia. METHODS: Relevant articles were identified through searches of PubMed, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews by using the terms niacin, omega-3 fatty acids (FAs), clofibrate, fibrate, fenofibrate, fenofibric acid, gemfibrozil, cholestyramine, colestipol, colesevelam, ezetimibe, proprotein convertase subtilisin/kexin 9 (PCSK9), cholesteryl ester transfer protein (CETP), and cardiovascular outcomes. Only English language, human clinical trials, meta-analyses, and systematic reviews were included. Additional references were identified from citations of published articles. FINDINGS: Niacin may reduce cardiovascular events as monotherapy; however, recent trials in combination with statins have failed to show a benefit. Trials with omega-3 FAs have failed to demonstrate significant reductions in cardiovascular outcomes. Fibrates may improve cardiovascular outcomes as monotherapy; however, trials in combination with statins have failed to show a benefit, except in those with elevated triglycerides (>200 mg/dL) or low HDL-C (<40 mg/dL). There is a lack of data that evaluates bile acid sequestrant in combination with statin therapy on reducing cardiovascular events. Ezetimibe-statin combination therapy can reduce cardiovascular outcomes in those with chronic kidney disease and following vascular surgery or acute coronary syndrome. Long-term effects of emerging nonstatin therapies (CETP and PCSK9 inhibitors) are currently being evaluated in ongoing Phase III trials. IMPLICATIONS: Nonstatin therapies have a limited role in reducing cardiovascular events in those maintained on guideline-directed statin therapy. In certain clinical situations, such as patients who are unable to tolerate statin therapy or recommended intensities of statin therapy, those with persistent severe elevations in triglycerides, or patients with high cardiovascular risk, some nonstatin therapies may be useful in reducing cardiovascular events. Future research is needed to evaluate the role of nonstatin therapies in those who are unable to tolerate guideline-directed statin doses.

Maternal health and pregnancy outcomes comparing migrant women born in humanitarian and nonhumanitarian source countries: a retrospective, observational study.

BACKGROUND: The relationship between migration and pregnancy outcomes is complex, with little insight into whether women of refugee background have greater risks of adverse pregnancy outcomes than other migrant women. This study aimed to describe maternal health, pregnancy care, and pregnancy outcomes among migrant women from humanitarian and nonhumanitarian source countries. METHODS: Retrospective, observational study of singleton births, at a single maternity service in Australia 2002-2011, to migrant women born in humanitarian source countries (HSCs, n = 2,713) and non-HSCs (n = 10,606). Multivariable regression analysis assessed associations between maternal HSC-birth and pregnancy outcomes. RESULTS: Compared with women from non-HSCs, the following were more common in women from HSCs: age < 20 years (0.6 vs 2.9% p < 0.001), multiparity (51 vs 76% p < 0.001), body mass index (BMI) ≥ 25 (38 vs 50% p < 0.001), anemia (3.2 vs 5.9% p < 0.001), tuberculosis (0.1 vs 0.4% p = 0.001), and syphilis (0.4 vs 2.5% p < 0.001). Maternal HSC-birth was independently associated with poor or no pregnancy care attendance (OR 2.5 [95% CI 1.8-3.6]), late first pregnancy care visit (OR 1.3 [95% CI 1.1-1.5]), and postterm birth (> 41 weeks gestation) (OR 2.5 [95% CI 1.9-3.4]). Stillbirth (0.8 vs 1.2% p = 0.04, OR 1.5 [95% CI 1.0-2.4]) and unplanned birth before arrival at the hospital (0.6 vs 1.2% p < 0.001, OR 1.3 [95% CI 0.8-2.1]) were more common in HSC-born women but not independently associated with maternal HSC-birth after adjusting for age, parity, BMI and relative socioeconomic disadvantage. CONCLUSIONS: These findings suggest areas where women from HSCs may have additional needs in pregnancy compared with women from non-HSCs. Refugee-focused strategies to support engagement in pregnancy care and address maternal health needs would be expected to improve health outcomes in resettlement countries.

Vitamin D testing in pregnancy: Does one size fit all?

BACKGROUND: Vitamin D deficiency is common. What the optimum level of vitamin D in pregnancy and whether vitamin D supplementation in pregnancy confers improved health benefits remain controversial. AIM: To assess vitamin D status in pregnant women in a maternity service that recommends routine antenatal screening and advises supplementation where necessary, and to assess relationships between early pregnancy vitamin D levels and changes in vitamin D across pregnancy with pregnancy outcomes. MATERIALS AND METHODS: Vitamin D serum concentrations were measured in early and late pregnancy. The relationships between initial vitamin D status, maternal factors and pregnancy outcomes were estimated. Change in vitamin D over pregnancy was quantified. The relationship between change in vitamin D over pregnancy and pregnancy outcomes was also estimated. RESULTS: Of 1550 women, 849 (55%) were vitamin D deficient (<50 nmol/L), 571 (37%) were insufficient (50-74 nmol/L), and 130 (8%) were replete (≥75 nmol/L) in early pregnancy. Factors associated with deficiency were increased body mass index, pregnancy in either winter or spring months, and maternal country of birth (South-East, South and East Asia, and Africa). Vitamin D deficiency or insufficiency in early pregnancy was significantly associated with developing gestation diabetes mellitus. Levels of vitamin D significantly increased over pregnancy among nonreplete women. Increasing vitamin D over pregnancy was not related to pregnancy outcomes. CONCLUSION: Vitamin D 'deficiency' is common but may not be associated with most adverse pregnancy outcomes. Routine vitamin D testing of all pregnant women does not appear warranted.

Maternal health and pregnancy outcomes among women of refugee background from Asian countries.

OBJECTIVE: To compare maternal health, prenatal care, and pregnancy outcomes among women of refugee background (born in Asian humanitarian source countries [HSCs]) and non-refugee background (born in Asian non-HSCs) at Monash Health (Melbourne, VIC, Australia). METHODS: In a retrospective study, data were obtained for women born in HSCs and non-HSCs from the same region who received government-funded health care for singleton pregnancies between 2002 and 2011. Multivariable regression analyses assessed associations between maternal HSC origin and pregnancy outcomes. RESULTS: Data were included for 1930 women from South Asian HSCs and 7412 from non-HSCs, 107 from Southeast Asian HSCs and 5574 from non-HSCs, 287 from West Asian HSCs and 990 from non-HSCs. Overweight, anemia, and teenage pregnancy were generally more common in the HSC groups. Birth in an HSC was independently associated with poor/no pregnancy care attendance (OR 4.2; 95% CI 2.5-7.3), late booking visit (OR 1.3; 95% CI 1.1-1.5), and post-term birth (OR 3.0; 95% CI 2.0-4.5) among women from South Asia. For Southeast Asia, HSC birth was independently associated with labor induction (OR 2.0; 95% CI 1.1-3.5). No independent associations were recorded for West Asia. CONCLUSION: Women born in Afghanistan, Bhutan, Iraq, and Myanmar had poorer general maternal health. Those from South Asian HSCs had increased risks of lower engagement in prenatal care, and post-term birth.

Maternal health and pregnancy outcomes among women of refugee background from African countries: a retrospective, observational study in Australia.

BACKGROUND: Women of refugee background from Africa are reported to have a greater risk of adverse pregnancy outcomes compared to women born in resettlement countries. However, there is currently little insight into whether adverse pregnancy outcomes are more common among migrant women of refugee background, compared to women who have migrated for non-humanitarian reasons. To inform whether women of refugee background require additional services in pregnancy compared to non-refugee migrant women from similar world regions we aimed to describe and compare maternal health, pregnancy care attendance and pregnancy outcomes among migrant women from Africa with or without a refugee background. METHODS: Retrospective, observational study of singleton births at a single, metropolitan, maternity service in Australia 2002-2011, to women born in humanitarian source countries (HSC) and non-HSC from North Africa (n = 1361), Middle and East Africa (n = 706) and West Africa (n = 106). RESULTS: Compared to non-HSC groups, age < 20 years (0-1.4% vs 2.3-13.3%), living in relatively socio-economically disadvantaged geographic areas (26.2-37.3% vs 52.9-77.8%) and interpreter need (0-23.9% vs 9.7-51.5%) were generally more common in the HSC groups. Compared to non-HSC groups, female genital mutilation (0.3-3.3% vs 5.1-13.8%), vitamin D insufficiency (8.7-21.5% vs 23.3-32.0%), syphilis (0-0.3% vs 1.2-7.5%) and hepatitis B (0-1.1% vs 1.2-18%) were also generally more common among the HSC groups. Unplanned birth before arrival at the hospital (3.6%) was particularly high in the North African HSC group. HSC-birth was associated with gestational diabetes mellitus (odds ratio = 3.5, 95% confidence interval: 1.8-7.1) among women from Middle and East Africa, after adjusting for maternal age, parity, body mass index and relative socio-economic disadvantage of area of residence. The West African HSC group had the highest stillbirth incidence (4.4%). CONCLUSIONS: Migrant women of refugee background from different African regions appear to be at greater risk of specific adverse pregnancy outcomes compared to migrant women without a refugee background. Awareness of differing risks and health needs would assist provision of appropriate pregnancy care to improve the health of African women and their babies.

Clinical evaluation of the Nucleus 6 cochlear implant system: performance improvements with SmartSound iQ.

OBJECTIVE: This paper provides a detailed description of the Nucleus 6 system, and clinically evaluates user performance compared to the previous Nucleus 5 system in cochlear implant recipients. Additionally, it clinically evaluates a range of Nucleus 6 and Nucleus 5 programs to determine the performance benefits provided by new input processing technologies available in SmartSound iQ. DESIGN: Speech understanding tests were used to clinically validate the default Nucleus 6 program, by comparing performance outcomes against up to five custom Nucleus 5 or Nucleus 6 programs in a range of listening environments. Clinical comparisons between programs were conducted across the following listening environments; quiet, speech weighted noise (co-located and spatially separated noise), and 4-talker babble (co-located and spatially separated noise). STUDY SAMPLE: Twenty-one adult cochlear implant recipients participated. RESULTS: Significant speech understanding benefits were found with the default Nucleus 6 program compared to the participants' preferred program using their Nucleus 5 processor and compared to a range of custom Nucleus 6 programs. All participants successfully accepted and upgraded to the new default Nucleus 6 SmartSound iQ program. CONCLUSION: This study demonstrates the acceptance and clinical benefits of the Nucleus 6 cochlear implant system and SmartSound iQ.

Is place of birth associated with mode of birth? The effect of hospital on caesarean section rates in a public metropolitan health service.

BACKGROUND: The effects of place of birth on birth outcomes have been examined in several studies both locally and internationally. However, none has examined the impact on caesarean section rates of different level maternity hospitals operating within the one health service. This study aimed to examine the impact of place of (Hospital level 6; 4-5 or 4) on birth outcomes in a large metropolitan health service in Victoria. METHODS: A cross-sectional study utilising data on births to low-risk first-time mothers during 2010-2011. Data were obtained from the Birthing Outcome System (BOS) database of Monash Health. Unadjusted and adjusted analyses were undertaken using logistic regression to examine the association between place of birth and caesarean section. RESULTS: In this group of low-risk nulliparae, there was evidence of a significant association between place of birth and caesarean section. The lower the acuity of the hospital, the higher the odds for the caesarean section. Compared with the level 6 hospital, the AdjOR for caesarean section at the level 4 hospital was 1.81 (95% CI: 1.37-2.41) and at the level 4-5 hospital, 1.30 (95% CI: 1.0-1.7). CONCLUSIONS: Low-risk nulliparae in spontaneous labour giving birth at the level 4 hospital in this health service are at significantly increased risk of caesarean section. This may have implications for the organisation and resource management of other level 4 public maternity units. Care in a tertiary (level 6) service may not necessarily equate to the higher rates of intervention reported by others.

Plate-based diversity subset screening: an efficient paradigm for high throughput screening of a large screening file.

The screening files of many large companies, including Pfizer, have grown considerably due to internal chemistry efforts, company mergers and acquisitions, external contracted synthesis, or compound purchase schemes. In order to screen the targets of interest in a cost-effective fashion, we devised an easy-to-assemble, plate-based diversity subset (PBDS) that represents almost the entire computed chemical space of the screening file whilst comprising only a fraction of the plates in the collection. In order to create this file, we developed new design principles for the quality assessment of screening plates: the Rule of 40 (Ro40) and a plate selection process that insured excellent coverage of both library chemistry and legacy chemistry space. This paper describes the rationale, design, construction, and performance of the PBDS, that has evolved into the standard paradigm for singleton (one compound per well) high-throughput screening in Pfizer since its introduction in 2006.

Ethnicity and the risk of late-pregnancy stillbirth.

OBJECTIVE: To determine if maternal country of birth is associated with the risk of antepartum stillbirth in late pregnancy. DESIGN, SETTING AND PARTICIPANTS: Retrospective cross-sectional study of all singleton births at 37-42 weeks' gestation, excluding those with congenital abnormalities and intrapartum stillbirths, between 1 June 2001 and 31 May 2011 at Southern Health, a large metropolitan maternity service in Melbourne, Australia. MAIN OUTCOME MEASURE: Rate of late-pregnancy antepartum stillbirth, analysed by maternal country of birth. RESULTS: Among 44 326 births, there was a significant difference in the stillbirth rate by maternal country of birth (P < 0.001). The rate of stillbirth per 1000 births was 1.48 among Australian-born women, 3.55 among South Asian-born women and 1.06 among South-East-East Asian-born women. Women born in South Asia were 2.4 (95% CI, 1.4-4.0) times more likely to have a late-pregnancy stillbirth than women born in Australia (P < 0.001). There was no significant difference between women born in Australia and women born in South-East-East Asia (P = 0.34). Adjusting for potential confounding factors, South Asian maternal birth remained an independent risk factor for stillbirth (adjusted odds ratio, 2.5; 95% CI, 1.3-5.1; P = 0.009). CONCLUSION: Women born in South Asia have an increased risk of antepartum stillbirth in late pregnancy, compared with other women. This observation may have implications for the delivery of pregnancy care in Australia.

Psychophysical measures in patients fitted with Contour and straight Nucleus electrode arrays.

The objective of this study was to compare the psychophysical performance of patients using the Nucleus Contour electrode array with that of patients using the straight banded-electrode array. In particular, we wished to consider how psychophysical parameters would differ for an electrode array positioned closer to the modiolus, and how this might influence both patient benefits and the design of speech processing strategies. Nine subjects participated in the study: four used the Nucleus straight array and five used the Nucleus Contour electrode array. Radiographic analyses found that the Contour array lay closer to the modiolus, was more deeply inserted and spanned a larger fractional length of the basilar membrane than the straight banded-electrode array. The results were analysed in terms of array type and of the position of the individual electrode band, both distance from the modiolus and longitudinal placement. Mean threshold was lower for the Contour array but maximum comfortable level was similar. Whereas threshold varied significantly with distance of electrode band from the modiolus, maximum comfortable level did not. Pitch varied fairly regularly with longitudinal position of the stimulated electrode, with the exception of one Contour subject. The forward masking profiles, using moderately loud maskers, were narrower for the Contour array, indicative of more localized neural excitation.

Evaluation of streamlined programming procedures for the Nucleus cochlear implant with the Contour electrode array.

OBJECTIVE: The objective of this study was to evaluate streamlined programming procedures for the Nucleus cochlear implant system with the Contour electrode array. DESIGN: Phase 1 involved an examination of the clinical MAPs for the first 103 recipients implanted with the Contour electrode array in the Melbourne Cochlear Implant Clinic, to examine the ability to predict the entire MAP based on a smaller number of clinically determined T- and/or C-levels. In phase 2, a subset of the streamlined procedures was selected and clinically evaluated, using speech perception and subjective preference measures. In the first study, the clinical MAP was compared with a MAP based on interpolating across three behavioral T-levels and three behavioral C-levels in a group of newly implanted subjects. The second study investigated the use of a single interpolated profile as the basis to creating the entire MAP. Initial evaluation compared the clinical MAP with two streamlined MAPs, one in which the C-level profile was derived from interpolation across a subset of T-levels and one in which the T-level profile was derived from interpolation across a subset of C-levels. In this case, the interpolated profile was based on five behavioral measures. Subsequently, the use of either three or a single T-level measure as the basis for the interpolated T-level profile was evaluated. Eighteen subjects, who were experienced with the clinical MAP before enrollment in the study, participated in the initial evaluation. The subjects were selected to include a group whose RMS deviation from clinical MAP levels, as determined in Phase 1, was greater than that of the wider population. RESULTS: The Phase 1 analysis showed that as expected, larger differences were observed between the clinical and derived MAP levels as interpolation was applied across fewer measured electrodes and that the use of a single interpolated profile to create the entire MAP resulted in the greatest deviation. No significant group mean difference was found in speech perception scores for newly implanted subjects when mapped with the clinical versus the streamlined MAP based on three behavioral T- and three behavioral C-level measures. For some individual subjects, scores were higher with the streamlined MAP. Subjective reports from the comparative performance questionnaire were consistent with these findings. No significant group mean difference in speech perception scores was found in comparing the clinical MAP with the streamlined MAPs based on a single interpolated T- or C-level profile created from five behavioral measures. Individual effects were observed; however, there was no consistent finding across subjects. The use of three rather than five behavioral T-level measures in the procedure did not result in significantly lower group mean scores; however, significantly poorer scores were obtained for three of the 10 individual subjects. The use of a MAP based on a single behavioral measure did result in poorer speech perception scores when compared with the MAP based on five behavioral T-level measures. These findings were consistent with subjective results from the performance questionnaires administered to determine preference for program across a range of listening situations. CONCLUSIONS: Two streamlined programming procedures are recommended for use in the clinical setting: (1) interpolating across three measured T-levels and three measured C-levels and (2) interpolating across five measured T- or C-levels and using the interpolated profile for fitting of the alternative profile.

Threshold, comfortable level and impedance changes as a function of electrode-modiolar distance.

OBJECTIVE: The study investigated the hypothesis that threshold and comfortable levels recorded from cochlear implant patients would reduce, and dynamic range increase, as distance of the electrode from the modiolar wall (radial distance) decreases. Two groups of cochlear implant patients participated; one group using the Nucleus' 24 Contour electrode array, and one group using the Nucleus standard straight (banded) array. The Nucleus 24 Contour array has been shown in temporal bone studies to lie closer to the modiolus than the banded array. The relationship of electrode impedance and radial distance is also investigated. DESIGN: The study, conducted at three centers, evaluated 21 patients using the Contour array, and 36 patients using the banded array. For each patient, threshold, comfortable levels and dynamic range were measured at four time points. Common ground electrode impedance was recorded clinically from each patient, at time intervals up to 12 wk. An estimate of the radial distance of the electrode from the modiolus was made by analysis of Cochlear view x-rays. RESULTS: Threshold and comfortable levels were significantly lower for the Nucleus 24 Contour array than for the banded array. However, dynamic range measurements did not show the predicted increase. In a majority of subjects, a significant correlation was found between the estimated radial distance of the electrode from the modiolus and the measured threshold and comfortable levels. This trend was not observed for dynamic range. The analysis indicates that other factors than radial distance are involved in the resultant psychophysical levels. Clinical impedance measures (common ground) were found to be significantly higher for the Contour array. However, the electrodes on the Contour array are half-rings, which are approximately only half the geometric size of the full rings as electrodes of the standard array. When the geometric electrode area in the two array designs are normalized, the trends in the electrode impedance behavior are similar. CONCLUSIONS: The results support the hypothesis that the relationship between the radial distance of the electrode and the psychophysical measures are influenced by patterns of fibrous tissue growth and individual patient differences, such as etiology and neural survival. Impedance measures for the Nucleus 24 Contour electrode array were higher than the banded electrode array, but this is primarily due to the reduction in electrode surface area. The different outcomes in impedance over time suggest differences in the relative contributions of the components of impedance with the two arrays.