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1.  The Architecture of Provider-Parent Vaccine Discussions at Health Supervision Visits 
Pediatrics  2013;132(6):1037-1046.
OBJECTIVE:
To characterize provider-parent vaccine communication and determine the influence of specific provider communication practices on parent resistance to vaccine recommendations.
METHODS:
We conducted a cross-sectional observational study in which we videotaped provider-parent vaccine discussions during health supervision visits. Parents of children aged 1 to 19 months old were screened by using the Parent Attitudes about Childhood Vaccines survey. We oversampled vaccine-hesitant parents (VHPs), defined as a score ≥50. We developed a coding scheme of 15 communication practices and applied it to all visits. We used multivariate logistic regression to explore the association between provider communication practices and parent resistance to vaccines, controlling for parental hesitancy status and demographic and visit characteristics.
RESULTS:
We analyzed 111 vaccine discussions involving 16 providers from 9 practices; 50% included VHPs. Most providers (74%) initiated vaccine recommendations with presumptive (eg, “Well, we have to do some shots”) rather than participatory (eg, “What do you want to do about shots?”) formats. Among parents who voiced resistance to provider initiation (41%), significantly more were VHPs than non-VHPs. Parents had significantly higher odds of resisting vaccine recommendations if the provider used a participatory rather than a presumptive initiation format (adjusted odds ratio: 17.5; 95% confidence interval: 1.2–253.5). When parents resisted, 50% of providers pursued their original recommendations (eg, “He really needs these shots”), and 47% of initially resistant parents subsequently accepted recommendations when they did.
CONCLUSIONS:
How providers initiate and pursue vaccine recommendations is associated with parental vaccine acceptance.
doi:10.1542/peds.2013-2037
PMCID: PMC3838535  PMID: 24190677
immunization; health communication; preventive health services
2.  Updated Approach for the Assessment of Ventilator Associated Pneumonia 
Critical care medicine  2013;41(11):10.1097/CCM.0b013e3182a84be1.
doi:10.1097/CCM.0b013e3182a84be1
PMCID: PMC3828199  PMID: 24162675
Pneumonia; Ventilator-Associated; Guidelines
3.  The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on neonatal health outcomes: the LIMIT randomised trial 
BMC Medicine  2014;12(1):163.
Background
Overweight and obesity during pregnancy represents a considerable health burden. While research has focused on interventions to limit gestational weight gain, there is little information describing their impact on neonatal health. Our aim was to investigate the effect on a range of pre-specified secondary neonatal outcomes of providing antenatal dietary and lifestyle advice to women who are overweight or obese.
Methods
We report a range of pre-specified secondary neonatal outcomes from a large randomised trial in which antenatal dietary and lifestyle advice was provided to women who were overweight or obese. Pregnant women were eligible for participation with a body mass index of 25 kg/m2 or over, and singleton gestation between 10+0 and 20+0 weeks. Outcome measures included gestational age at birth; Apgar score below 7 at 5 minutes of age; need for resuscitation at birth; birth weight above 4.5 kg or below 2.5 kg; birth weight, length and head circumference (and Z-scores); admission to the nursery; respiratory distress syndrome; and postnatal length of stay. Data relating to the primary outcome (large for gestational age infants defined as birth weight above the 90th centile) and birth weight above 4 kg have been reported previously. Analyses used intention-to-treat principles.
Results
In total, 2,142 infants were included in the analyses. Infants born to women following lifestyle advice were significantly less likely to have birth weight above 4.5 kg (2.15% versus 3.69%; adjusted risk ratio (aRR) = 0.59; 95% confidence interval (CI) 0.36 to 0.98; P = 0.04), or respiratory distress syndrome (1.22% versus 2.57%; aRR = 0.47; 95% CI 0.24 to 0.90; P = 0.02), particularly moderate or severe disease, and had a shorter length of postnatal hospital stay (3.94 ± 7.26 days versus 4.41 ± 9.87 days; adjusted ratio of means 0.89; 95% CI 0.82 to 0.97; P = 0.006) compared with infants born to women who received Standard Care.
Conclusions
For women who are overweight or obese, antenatal dietary and lifestyle advice has health benefits for infants, without an increase in the risk of harm. Continued follow-up into childhood will be important to assess the longer-term effects of a reduction in high infant birth weight on risk of child obesity.
Please see related articles: http://www.biomedcentral.com/1741-7015/12/161 and http://www.biomedcentral.com/1741-7015/12/201.
Clinical trial registration
Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426)
doi:10.1186/s12916-014-0163-9
PMCID: PMC4194368  PMID: 25315325
Pregnancy; Overweight and obesity; Neonatal health; Randomised trial; Dietary and lifestyle intervention
4.  The effects of antenatal dietary and lifestyle advice for women who are overweight or obese on maternal diet and physical activity: the LIMIT randomised trial 
BMC Medicine  2014;12(1):161.
Background
Overweight and obesity is a significant health concern during pregnancy. Our aim was to investigate the effect of providing antenatal dietary and lifestyle advice to women who are overweight or obese on components of maternal diet and physical activity.
Methods
We conducted a randomised controlled trial, in which pregnant women with a body mass index ≥25 kg/m2, and singleton gestation between 10+0 to 20+0 weeks were recruited and randomised to Lifestyle Advice (involving a comprehensive dietary and lifestyle intervention over their pregnancy) or Standard Care. Within the intervention group, we conducted a nested randomised trial in which a subgroup of women were further randomised to receive access to supervised group walking sessions in addition to the standard information presented during the intervention contacts (the Walking group) or standard information only.
The outcome measures were maternal dietary intake, (including food groups, macronutrient and micronutrient intake, diet quality (using the Healthy Eating Index; HEI), dietary glycaemic load, and glycaemic index) and maternal physical activity. Women completed the Harvard Semi-Structured Food Frequency Questionnaire, and the Short Questionnaire to Assess Health-enhancing Physical Activity (SQUASH), at trial entry, 28 and 36 weeks’ gestational age, and 4 months postpartum.
Analyses were performed on an intention-to-treat basis, using linear mixed effects models with adjustment for the stratification variables.
Results
Women randomised to Lifestyle Advice demonstrated a statistically significant increase in the number of servings of fruit and vegetables consumed per day, as well as increased consumption of fibre, and reduced percentage energy intake from saturated fats (P < 0.05 for all). Maternal HEI was significantly improved at both 28 (73.35 ± 6.62 versus 71.86 ± 7.01; adjusted difference in means 1.58; 95% CI 0.89 to 2.27; P < 0.0001) and 36 (72.95 ± 6.82 versus 71.17 ± 7.69; adjusted difference in means 1.77; 95% CI 1.01 to 2.53; P < 0.0001) weeks. There were no differences in dietary glycaemic index or glycaemic load. Women randomised to Lifestyle Advice also demonstrated greater total physical activity (adjusted difference in means 359.76 metabolic equivalent task units (MET) minutes/week; 95% CI 74.87 to 644.65; P = 0.01) compared with women receiving Standard Care. The supervised walking group was poorly utilised.
Conclusions
For women who are overweight or obese, antenatal lifestyle advice improves maternal diet and physical activity during pregnancy.
Please see related articles: http://www.biomedcentral.com/1741-7015/12/163 and http://www.biomedcentral.com/1741-7015/12/201.
Trial registration
Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426)
Electronic supplementary material
The online version of this article (doi:10.1186/s12916-014-0161-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12916-014-0161-y
PMCID: PMC4194375  PMID: 25315237
Pregnancy; Overweight and obesity; Diet composition; Physical activity; Randomised trial; Dietary and lifestyle intervention
5.  Challenges to Protocol Optimization Due to Unexpected Variation of CT Contrast Dose Amount and Flow 
Journal of Digital Imaging  2012;26(3):402-405.
High-quality computed tomography (CT) exams are critical to maximizing radiologist’s interpretive ability. Exam quality in part depends on proper contrast administration. We examined injector data from consecutive abdominal and pelvic CT exams to analyze variation in contrast administration. Discrepancies between intended IV contrast dose and flow rate with the actual administered contrast dose and measured flow rate were common. In particular, delivered contrast dose discrepancies of at least 10% occurred in 13% of exams while discrepancies in flow rate of at least 10% occurred in 42% of exams. Injector logs are useful for assessing and tracking this type of variability which may confound contrast administration optimization and standardization efforts.
doi:10.1007/s10278-012-9544-9
PMCID: PMC3649061  PMID: 23143417
Computed tomography; Computer communication networks; Computer hardware; Contrast media; Diagnostic image quality
6.  Implementation of the ACR Dose Index Registry at a Large Academic Institution: Early Experience 
Journal of Digital Imaging  2012;26(2):309-315.
A rising conciousness within both the medical community and in the public has been created by the current levels of radiation exposure from increased use of computed tomography. The concern has prompted the need for more data collection and analysis of hospital and imaging center exam doses. This has spurred the American College of Radiology (ACR) to develop the Dose Index Registry (DIR), which will allow participating insitutions to compare the radiation dose from their CT exams to aggregate national CT dose data based on exam type and body part. We outline the steps involved in the process of enrolling in the DIR, the technical requirements, the challenges we encountered, and our solutions to those challenges. A sample of the quaterly report released by the ACR is presented and discussed. Enrolling in the ACR dose registry is a team effort with participation from IT, a site physicist, and a site radiologist. Participation in this registry is a great starting point to initiate a QA process for monitoring CT dose if none has been established at an institution. The ACR has developed an excellent platform for gathering, analyzing, and reporting CT dose data. Even so, each insititutions will have its own unique issues in joining the project.
doi:10.1007/s10278-012-9546-7
PMCID: PMC3597962  PMID: 23152117
Computed tomography; Radiation dose; Quality assurance
7.  Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial 
Objective To determine the effect of antenatal dietary and lifestyle interventions on health outcomes in overweight and obese pregnant women.
Design Multicentre randomised trial. We utilised a central telephone randomisation server, with computer generated schedule, balanced variable blocks, and stratification for parity, body mass index (BMI) category, and hospital.
Setting Three public maternity hospitals across South Australia.
Participants 2212 women with a singleton pregnancy, between 10+0 and 20+0 weeks’ gestation, and BMI ≥25.
Interventions 1108 women were randomised to a comprehensive dietary and lifestyle intervention delivered by research staff; 1104 were randomised to standard care and received pregnancy care according to local guidelines, which did not include such information.
Main outcome measures Incidence of infants born large for gestational age (birth weight ≥90th centile for gestation and sex). Prespecified secondary outcomes included birth weight >4000 g, hypertension, pre-eclampsia, and gestational diabetes. Analyses used intention to treat principles.
Results 2152 women and 2142 liveborn infants were included in the analyses. The risk of the infant being large for gestational age was not significantly different in the two groups (lifestyle advice 203/1075 (19%) v standard care 224/1067 (21%); adjusted relative risk 0.90, 95% confidence interval 0.77 to 1.07; P=0.24). Infants born to women after lifestyle advice were significantly less likely to have birth weight above 4000 g (lifestyle advice 164/1075 (15%) v standard care 201/1067 (19%); 0.82, 0.68 to 0.99; number needed to treat (NNT) 28, 15 to 263; P=0.04). There were no differences in maternal pregnancy and birth outcomes between the two treatment groups.
Conclusions For women who were overweight or obese, the antenatal lifestyle advice used in this study did not reduce the risk delivering a baby weighing above the 90th centile for gestational age and sex or improve maternal pregnancy and birth outcomes.
Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12607000161426).
doi:10.1136/bmj.g1285
PMCID: PMC3919179  PMID: 24513442
8.  Pitfalls in Diagnosis: Suspected Anomalous Origin of the Right Coronary Artery from the Pulmonary Artery 
Texas Heart Institute Journal  2014;41(1):51-54.
Anomalous coronary arteries are rare in the general population. We report the case of a term neonate who underwent an echocardiogram to evaluate a possible patent ductus arteriosus. Unexpectedly, an apparent anomalous origin of the right coronary artery from the main pulmonary artery was detected by surface 2-dimensional transthoracic echocardiography and color-flow Doppler imaging. Because ventricular size and function were normal, the patient ultimately underwent cardiac catheterization to verify the anatomy before proposed surgery. Angiograms showed that the right coronary artery arose from the left anterolateral portion of the mid-ascending aorta. The patient did not require surgery. This case report illustrates pitfalls that can occur in the diagnosis of coronary artery anomalies.
doi:10.14503/THIJ-13-3363
PMCID: PMC3967489  PMID: 24512400
Aorta/abnormalities; coronary angiography; coronary vessel anomalies/diagnosis/radiography; echocardiography, transthoracic; heart defects, congenital; infant; male
9.  Consultations Between Patients With Breast Cancer and Surgeons: A Pathway From Patient-Centered Communication to Reduced Hopelessness  
Journal of Clinical Oncology  2012;31(3):351-358.
Purpose
Patient-centered communication (PCC) affects psychosocial health outcomes of patients. However, these effects are rarely direct, and our understanding of such effects are largely based on self-report (v observational) data. More information is needed on the pathways by which concrete PCC behaviors affect specific psychosocial outcomes in cancer care. We hypothesized that PCC behaviors increase the satisfaction of patients with surgeons, which, in turn, reduces the postconsultation hopelessness of patients.
Patients and Methods
In Portland, OR, we videotaped consultations between 147 women newly diagnosed with breast cancer and nine surgeons and administered surveys to participants immediately preconsultation and postconsultation. Consultations were coded for PCC behaviors. Multivariate regression models analyzed the association between PCC and the satisfaction of patients and between satisfaction and hopelessness.
Results
Levels of hopelessness of patients significantly decreased from preconsultation to postconsultation (P < .001). Two PCC behaviors (ie, patient asserting treatment preference [odds ratio {OR}, 1.50/log unit; 95% CI, 1.01 to 2.23/log unit; P = .042] and surgeon providing good/hopeful news [OR, 1.62/log unit; 95% CI, 1.01 to 2.60/log unit; P = .047]) were independently significantly associated with the satisfaction of patients with surgeons, which, in turn, independently predicted reduced levels of postconsultation hopelessness (linear change, −0.78; 95% CI, 1.44 to −0.12; P = .02).
Conclusion
Although additional research is needed with larger and more-diverse data sets, these findings suggest the possibility that concrete and trainable PCC behaviors can lower the hopelessness of patients with breast cancer indirectly through their effects on patient satisfaction with care.
doi:10.1200/JCO.2012.44.2699
PMCID: PMC3732013  PMID: 23233706
10.  Aboriginal Families Study: a population-based study keeping community and policy goals in mind right from the start 
Background
Australian Aboriginal and Torres Strait Islander women are between two to five times more likely to die in childbirth than non-Aboriginal women, and two to three times more likely to have a low birthweight infant. Babies with a low birthweight are more likely to have chronic health problems in adult life. Currently, there is limited research evidence regarding effective interventions to inform new initiatives to strengthen antenatal care for Aboriginal families.
Method/Design
The Aboriginal Families Study is a cross sectional population-based study investigating the views and experiences of Aboriginal and non-Aboriginal women having an Aboriginal baby in the state of South Australia over a 2-year period. The primary aims are to compare the experiences and views of women attending standard models of antenatal care with those accessing care via Aboriginal Family Birthing Program services which include Aboriginal Maternal Infant Care (AMIC) Workers as members of the clinical team; to assess factors associated with early and continuing engagement with antenatal care; and to use the information to inform strengthening of services for Aboriginal families. Women living in urban, regional and remote areas of South Australia have been invited to take part in the study by completing a structured interview or, if preferred, a self-administered questionnaire, when their baby is between 4–12 months old.
Discussion
Having a baby is an important life event in all families and in all cultures. How supported women feel during pregnancy, how women and families are welcomed by services, how safe they feel coming in to hospitals to give birth, and what happens to families during a hospital stay and in the early months after the birth of a new baby are important social determinants of maternal, newborn and child health outcomes. The Aboriginal Families Study builds on consultation with Aboriginal communities across South Australia. The project has been implemented with guidance from an Aboriginal Advisory Group keeping community and policy goals in mind right from the start. The results of the study will provide a unique resource to inform quality improvement and strengthening of services for Aboriginal families.
doi:10.1186/1475-9276-12-41
PMCID: PMC3689616  PMID: 23767813
Antenatal care; Health inequalities; Indigenous health; Maternal health; Participatory research; Perinatal health outcomes
11.  The Skeptical Technophile: iPad Review 
Journal of Digital Imaging  2012;25(3):365-368.
doi:10.1007/s10278-012-9467-5
PMCID: PMC3348982  PMID: 22395796
12.  Australasian randomised trial to evaluate the role of maternal intramuscular dexamethasone versus betamethasone prior to preterm birth to increase survival free of childhood neurosensory disability (A*STEROID): study protocol 
Background
Both dexamethasone and betamethasone, given to women at risk of preterm birth, substantially improve short-term neonatal health, increase the chance of the baby being discharged home alive, and reduce childhood neurosensory disability, remaining safe into adulthood. However, it is unclear which corticosteroid is of greater benefit to mother and child.
This study aims to determine whether giving dexamethasone to women at risk of preterm birth at less than 34 weeks’ gestation increases the chance of their children surviving free of neurosensory disability at two years’ corrected age, compared with betamethasone.
Methods/Design
Design randomised, multicentre, placebo controlled trial.
Inclusion criteria women at risk of preterm birth at less than 34 weeks’ gestation with a singleton or twin pregnancy and no contraindications to the use of antenatal corticosteroids and who give informed consent.
Trial entry & randomisation at telephone randomisation eligible women will be randomly allocated to either the dexamethasone group or the betamethasone group, allocated a study number and corresponding treatment pack.
Study groups women in the dexamethasone group will be administered two syringes of 12 mg dexamethasone (dexamethasone sodium phosphate) and women in the betamethasone group will be administered two syringes of 11.4 mg betamethasone (Celestone Chronodose). Both study groups consist of intramuscular treatments 24 hours apart.
Primary study outcome death or any neurosensory disability measured in children at two years’ corrected age.
Sample size a sample size of 1449 children is required to detect either a decrease in death or any neurosensory disability from 27.0% to 20.1% with dexamethasone compared with betamethasone, or an increase from 27.0% to 34.5% (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2).
Discussion
This study will provide high-level evidence of direct relevance for clinical practice. If one drug clearly results in significantly fewer deaths and fewer disabled children then it should be used consistently in women at risk of preterm birth and would be of great importance to women at risk of preterm birth, their children, health services and communities.
Trial registration
Trial registration number: ACTRN12608000631303
doi:10.1186/1471-2393-13-104
PMCID: PMC3655914  PMID: 23642125
Antenatal corticosteroids; Dexamethasone; Betamethasone; Preterm birth; Randomised controlled trial; Neurosensory disability
13.  The IDEAL study: investigation of dietary advice and lifestyle for women with borderline gestational diabetes: a randomised controlled trial - study protocol 
Background
The Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) showed that treatment of pregnant women with mild gestational diabetes mellitus is beneficial for both women and their infants. It is still uncertain whether there are benefits of similar treatment for women with borderline gestational diabetes.
This trial aims to assess whether dietary and lifestyle advice and treatment given to pregnant women who screen for borderline gestational diabetes reduces neonatal complications and maternal morbidities.
Methods/design
Design: Multicentre, randomised controlled trial.
Inclusion criteria: Women between 240 and 346 weeks gestation with a singleton pregnancy, a positive oral glucose challenge test (venous plasma glucose ≥7.8 mmol/L) and a normal oral 75 gram glucose tolerance test (fasting venous plasma glucose <5.5 mmol/L and a 2 hour glucose <7.8 mmol/L) with written, informed consent.
Trial entry and randomisation: Women with an abnormal oral glucose tolerance test (fasting venous plasma glucose ≥5.5 mmol/L or 2 hour glucose ≥7.8 mmol/L) will not be eligible and will be offered treatment for gestational diabetes, consistent with recommendations based on results of the ACHOIS trial. Eligible women will be randomised into either the ‘Routine Care Group’ or the ‘Intervention Group’.
Study groups: Women in the ‘Routine Care Group’ will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the ‘Intervention Group’ will receive obstetric care, which will include dietary and lifestyle advice, monitoring of blood glucose and further medical treatment for hyperglycaemia as appropriate.
Primary study outcome: Incidence of large for gestational age infants.
Sample size: A sample size of 682 women will be sufficient to show a 50% reduction in the risk of large for gestational age infants (alpha 0.05 two-tailed, 80% power, 4% loss to follow up) from 14% to 7% with dietary and lifestyle advice and treatment.
Discussion
A conclusive trial outcome will provide reliable evidence of relevance for the care of women with borderline glucose intolerance in pregnancy and their infants.
Trial registration
Australian New Zealand Clinical Trials Registry - ACTRN12607000174482
doi:10.1186/1471-2393-12-106
PMCID: PMC3506505  PMID: 23046499
Borderline gestational diabetes; Gestational diabetes mellitus; Randomised controlled trial; Diet; Lifestyle; Large for gestational age
14.  Planned Vaginal Birth or Elective Repeat Caesarean: Patient Preference Restricted Cohort with Nested Randomised Trial 
PLoS Medicine  2012;9(3):e1001192.
A study conducted in Australia provides new data on the outcomes for mother and baby associated with either planned vaginal birth, or elective repeat caesarean section following a previous caesarean section.
Background
Uncertainty exists about benefits and harms of a planned vaginal birth after caesarean (VBAC) compared with elective repeat caesarean (ERC). We conducted a prospective restricted cohort study consisting of a patient preference cohort study, and a small nested randomised trial to compare benefits and risks of a planned ERC with planned VBAC.
Methods and findings
2,345 women with one prior caesarean, eligible for VBAC at term, were recruited from 14 Australian maternity hospitals. Women were assigned by patient preference (n = 2,323) or randomisation (n = 22) to planned VBAC (1,225 patient preference, 12 randomised) or planned ERC (1,098 patient preference, ten randomised). The primary outcome was risk of fetal death or death of liveborn infant before discharge or serious infant outcome. Data were analysed for the 2,345 women (100%) and infants enrolled.
The risk of fetal death or liveborn infant death prior to discharge or serious infant outcome was significantly lower for infants born in the planned ERC group compared with infants in the planned VBAC group (0.9% versus 2.4%; relative risk [RR] 0.39; 95% CI 0.19–0.80; number needed to treat to benefit 66; 95% CI 40–200). Fewer women in the planned ERC group compared with women in the planned VBAC had a major haemorrhage (blood loss ≥1,500 ml and/or blood transfusion), (0.8% [9/1,108] versus 2.3% [29/1,237]; RR 0.37; 95% CI 0.17–0.80).
Conclusions
Among women with one prior caesarean, planned ERC compared with planned VBAC was associated with a lower risk of fetal and infant death or serious infant outcome. The risk of major maternal haemorrhage was reduced with no increase in maternal or perinatal complications to time of hospital discharge. Women, clinicians, and policy makers can use this information to develop health advice and make decisions about care for women who have had a previous caesarean.
Trial registration
Current Controlled Trials ISRCTN53974531
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Rates of caesarean section are rising around the world, particularly in high- and middle-income countries, where most women have a choice of how their baby is delivered. Historically, the obstetrician in charge of the woman's care made the decision on whether to perform an elective (planned) caesarean section based on medical criteria. For women who have had a previous caesarean section, typically, their options for mode of childbirth are either a trial of vaginal birth or an elective repeat caesarean section. The proportion of women attempting a vaginal birth after a previous caesarean section has been declining in many countries partly due to the variable chance of achieving a successful vaginal birth (reported between 56% and 80%) and partly because of negative reports of the risk of complications, both to the mother and the baby, of a having a vaginal delivery following a caesarean section. Consequently, the rates of repeat caesarean section have risen sharply, for example, currently 83% in Australia and almost 90% in the US.
Why Was This Study Done?
Both elective repeat caesarean section and subsequent vaginal delivery after a previous caesarean section have clinical risks and benefits. Most obviously, having a surgical procedure puts the woman having the repeat caesarean section at risk of surgical complications, especially if performed under a general anesthetic, and her baby may be at risk of respiratory complications. However, subsequent vaginal delivery following a previous caesarean section may put the mother at risk of bleeding severely enough to need a blood transfusion (more than 1,500 ml blood loss) and she may also be at increased risk of rupturing her uterus; and her baby may have an increased risk of dying or of becoming brain damaged due to lack of oxygen.
However, to date there have been no randomized controlled trials of elective repeat caesarean section versus vaginal delivery following a previous caesarean section to compare the health outcomes of mother and baby and a recent systematic review could draw no conclusions. So the researchers conducted this prospective cohort study based on patient preference (with a few women agreeing to be randomized to mode of delivery), to compare the health outcomes for mother and baby for elective repeat caesarean section versus vaginal delivery in women following a previous caesarean section.
What Did the Researchers Do and Find?
Between 2002 and 2007, the researchers recruited 2,345 suitable women (that is, women who had one previous caesarean section, were currently 37 weeks pregnant with a single baby, and who were clinically able to have a vaginal delivery) from 14 maternity hospitals throughout Australia. A few women (22) agreed to be randomized to either mode of delivery but most women chose her preferred option. Then, depending on the woman's preferences for mode of birth, participating obstetricians either scheduled a date for an elective caesarean section (1,098 women) or assessed on-going suitability for the woman to have a planned vaginal delivery (1,225 women). However only 535 (43.2%) women who chose to have a vaginal birth were able to deliver this way because of failure to progress in labor or fetal distress: 334 of these women (27.0%) had to have an elective caesarean section and 368 women had to have an emergency caesarean section.
Although no women died, women who had a planned caesarean section experienced less severe bleeding than women who delivered vaginally. There were no infant deaths in those born by elective caesarean section but two unexplained stillbirths in the planned vaginal delivery group. There was also a reduced risk of nonfatal serious outcome before discharge from hospital for infants delivered by in the elective caesarean section. The researchers calculated that one infant death or near death would be prevented for every 66 elective caesarean sections performed in women who had a previous caesarean section.
What Do These Findings Mean?
These findings show that in women who had delivered by a previous caesarean section delivering their next baby by planned caesarean section was associated with less infant death and better health outcomes for the mother before she was discharged from the hospital compared to women who had a subsequent vaginal delivery. This information can be used by women, clinicians, and policy makers in helping to make decisions about the mode of subsequent deliveries and best care for women who have had a previous caesarean section.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001192.
This study is linked to a PLoS Medicine Research Article by Fitzpatrick and colleagues and a PLoS Medicine Perspective by Catherine Spong
The American Congress of Obstetricians and Gynecologists has information sheets for patients on caesarean sections and on vaginal birth after caesarean delivery
Childbirth Connection, a US-based not-for-profit organization, provides information about caesarean sections and about vaginal birth after caesarean
The National Childbirth Trust, a UK charity, provides information for parents on all aspects of pregnancy and birth, including caesarean sections and vaginal birth after caesarean delivery
The UK charity Healthtalkonline has personal stories from women making decisions about birth after a caesarean section
doi:10.1371/journal.pmed.1001192
PMCID: PMC3302845  PMID: 22427749
15.  Parental Information Seeking Following a Positive Newborn Screening for Cystic Fibrosis 
Journal of health communication  2010;15(8):880-894.
This investigation focused on the information-seeking behaviors of parents (N = 38) whose newborn had received a positive screening result for cystic fibrosis. Roughly half of the participants actively sought information about their child's potential disease prior to the clinic visit. The most common sources of information were the internet, pediatricians, and family physicians. Analysis of behavior during the clinic visit showed rates of question asking that were judged as low, but comparable to the results of other studies. It was observed that parents would occasionally collaborate in the production of a single question. More educated parents tended to produce such questions more frequently. Importantly, frequency of collaborative questions was positively correlated with enhanced knowledge of cystic fibrosis six weeks after the clinic visit and with apparent dissatisfaction with the counseling interaction.
doi:10.1080/10810730.2010.522226
PMCID: PMC3033770  PMID: 21170789
16.  Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial 
Background
Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes.
The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes.
Methods/Design
Design: Multicentred randomised, controlled trial.
Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit.
Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth.
Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies.
Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice.
Outcome assessors will be blinded to the allocated treatment group.
Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age).
Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed).
Discussion
This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.
Trial Registration
Australian and New Zealand Clinical Trials Registry ACTRN12607000161426
doi:10.1186/1471-2393-11-79
PMCID: PMC3219553  PMID: 22026403
17.  Effect of Treatment of Gestational Diabetes Mellitus on Obesity in the Next Generation 
Diabetes Care  2010;33(5):964-968.
OBJECTIVE
Gestational diabetes mellitus (GDM) may cause obesity in the offspring. The objective was to assess the effect of treatment for mild GDM on the BMI of 4- to 5-year-old children.
RESEARCH DESIGN AND METHODS
Participants were 199 mothers who participated in a randomized controlled trial of the treatment of mild GDM during pregnancy and their children. Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance program in the state of South Australia. The main outcome measure was age- and sex-specific BMI Z score based on standards of the International Obesity Task Force.
RESULTS
At birth, prevalence of macrosomia (birth weight ≥4,000 g) was 5.3% among the 94 children whose mothers were in the intervention group, and 21.9% among the 105 children in the routine care control group. At 4- to 5-years-old, mean (SD) BMI Z score was 0.49 (1.20) in intervention children and 0.41 (1.40) among controls. The difference between treatment groups was 0.08 (95% CI −0.29 to 0.44), an estimate minimally changed by adjustment for maternal race, parity, age, and socio-economic index (0.08 [−0.29 to 0.45]). Evaluating BMI ≥85th percentile rather than continuous BMI Z score gave similarly null results.
CONCLUSIONS
Although treatment of GDM substantially reduced macrosomia at birth, it did not result in a change in BMI at age 4- to 5-years-old.
doi:10.2337/dc09-1810
PMCID: PMC2858199  PMID: 20150300
18.  Stressful life events, social health issues and low birthweight in an Australian population-based birth cohort: challenges and opportunities in antenatal care 
BMC Public Health  2011;11:196.
Background
Investment in strategies to promote 'a healthy start to life' has been identified as having the greatest potential to reduce health inequalities across the life course. The aim of this study was to examine social determinants of low birthweight in an Australian population-based birth cohort and consider implications for health policy and health care systems.
Methods
Population-based survey distributed by hospitals and home birth practitioners to >8000 women six months after childbirth in two states of Australia. Participants were women who gave birth to a liveborn infant in Victoria and South Australia in September/October 2007. Main outcome measures included stressful life events and social health issues, perceived discrimination in health care settings, infant birthweight.
Results
4,366/8468 (52%) of eligible women returned completed surveys. Two-thirds (2912/4352) reported one or more stressful life events or social health issues during pregnancy. Women reporting three or more social health issues (18%, 768/4352) were significantly more likely to have a low birthweight infant (< 2500 grams) after controlling for smoking and other socio-demographic covariates (Adj OR = 1.77, 95% CI 1.1-2.8). Mothers born overseas in non-English speaking countries also had a higher risk of having a low birthweight infant (Adj OR = 1.85, 95% CI 1.2-2.9). Women reporting three or more stressful life events/social health issues were more likely to attend antenatal care later in pregnancy (OR = 2.06, 95% CI 1.3-3.1), to have fewer antenatal visits (OR = 2.17, 95% CI 1.4-3.4) and to experience discrimination in health care settings (OR = 2.69, 95% CI 2.2-3.3).
Conclusions
There is a window of opportunity in antenatal care to implement targeted preventive interventions addressing potentially modifiable risk factors for poor maternal and infant outcomes. Developing the evidence base and infrastructure necessary in order for antenatal services to respond effectively to the social circumstances of women's lives is long overdue.
doi:10.1186/1471-2458-11-196
PMCID: PMC3080815  PMID: 21450106
19.  Timing of birth for women with a twin pregnancy at term: a randomised controlled trial 
Background
There is a well recognized risk of complications for both women and infants of a twin pregnancy, increasing beyond 37 weeks gestation. Preterm birth prior to 37 weeks gestation is a recognized complication of a twin pregnancy, however, up to 50% of twins will be born after this time.
The aims of this randomised trial are to assess whether elective birth at 37 weeks gestation compared with standard care in women with a twin pregnancy affects the risk of perinatal death, and serious infant complications.
Methods/Design
Design: Multicentred randomised trial.
Inclusion Criteria: women with a twin pregnancy at 366 weeks or more without contraindication to continuation of pregnancy.
Trial Entry & Randomisation: Following written informed consent, eligible women will be randomised from 36+6 weeks gestation. The randomisation schedule uses balanced variable blocks, with stratification for centre of birth and planned mode of birth. Women will be randomised to either elective birth or standard care.
Treatment Schedules: Women allocated to the elective birth group will be planned for elective birth from 37 weeks gestation. Where the plan is for vaginal birth, this will involve induction of labour. Where the plan is for caesarean birth, this will involve elective caesarean section. For women allocated to standard care, birth will be planned for 38 weeks gestation or later. Where the plan is for vaginal birth, this will involve either awaiting the spontaneous onset of labour, or induction of labour if required. Where the plan is for caesarean birth, this will involve elective caesarean section (after 38 and as close to 39 weeks as possible).
Primary Study Outcome: A composite of perinatal mortality or serious neonatal morbidity.
Sample Size: 460 women with a twin pregnancy to show a reduction in the composite outcome from 16.3% to 6.7% with adjustment for the clustering of twin infants within mothers (p = 0.05, 80% power).
Discussion
This is a protocol for a randomised trial, the findings of which will contribute information about the optimal time of birth for women with an uncomplicated multiple pregnancy at and beyond 37 weeks gestation.
Clinical Trial Registration
Current Controlled Trials ISRCTN15761056
doi:10.1186/1471-2393-10-68
PMCID: PMC2978123  PMID: 20973989
20.  Widespread Occurrence of Non-Enzymatic Deamidations of Asparagine Residues in Yersinia pestis Proteins Resulting from Alkaline pH Membrane Extraction Conditions 
The open proteomics journal  2008;1:106-115.
Extraction of crude membrane fractions with alkaline solutions, such as 100–200 mM Na2CO3 (pH ~11), is often used to solubilize peripheral membrane proteins. Integral membrane proteins are largely retained in membrane pellets. We applied this method to the fractionation of membrane proteins of the plague bacterium Yersinia pestis. Extensive horizontal spot trains were observed in 2-DE gels. The pI values of the most basic spots part of such protein spot trains usually matched the computationally predicted pI values. Regular patterns of decreasing spot pI values and in silico analysis with the software ProMoST suggested `n-1' deamidations of asparagine (N) and/or glutamine (Q) side chains for `n' observed spots of a protein in a given spot train. MALDI-MS analysis confirmed the occurrence of deamidations, particularly in N side chains part of NG dipeptide motifs. In more than ten cases, tandem MS data for tryptic peptides provided strong evidence for deamidations, with y- and b-ion series increased by 1 Da following N-to-D substitutions. Horizontal spot trains in 2-DE gels were rare when alkaline extraction was omitted during membrane protein sample preparation. This study strongly supports the notion that exposure to alkaline pH solutions is a dominant cause of extensive N and Q side chain deamidations in proteins during sample preparation of membrane extracts. The modifications are of non-enzymatic nature and not physiologically relevant. Therefore, quantitative spot differences within spot trains in differential protein display experiments following the aforementioned sample preparation steps need to be interpreted cautiously.
doi:10.2174/1875039700801010106
PMCID: PMC2860289  PMID: 20428468
Alkaline membrane extraction; deamidation; membrane proteome; spot train; two-dimensional gel electrophoresis
21.  The Complete Genome Sequence of Haloferax volcanii DS2, a Model Archaeon 
PLoS ONE  2010;5(3):e9605.
Background
Haloferax volcanii is an easily culturable moderate halophile that grows on simple defined media, is readily transformable, and has a relatively stable genome. This, in combination with its biochemical and genetic tractability, has made Hfx. volcanii a key model organism, not only for the study of halophilicity, but also for archaeal biology in general.
Methodology/Principal Findings
We report here the sequencing and analysis of the genome of Hfx. volcanii DS2, the type strain of this species. The genome contains a main 2.848 Mb chromosome, three smaller chromosomes pHV1, 3, 4 (85, 438, 636 kb, respectively) and the pHV2 plasmid (6.4 kb).
Conclusions/Significance
The completed genome sequence, presented here, provides an invaluable tool for further in vivo and in vitro studies of Hfx. volcanii.
doi:10.1371/journal.pone.0009605
PMCID: PMC2841640  PMID: 20333302
22.  Genome Degradation in Brucella ovis Corresponds with Narrowing of Its Host Range and Tissue Tropism 
PLoS ONE  2009;4(5):e5519.
Brucella ovis is a veterinary pathogen associated with epididymitis in sheep. Despite its genetic similarity to the zoonotic pathogens B. abortus, B. melitensis and B. suis, B. ovis does not cause zoonotic disease. Genomic analysis of the type strain ATCC25840 revealed a high percentage of pseudogenes and increased numbers of transposable elements compared to the zoonotic Brucella species, suggesting that genome degradation has occurred concomitant with narrowing of the host range of B. ovis. The absence of genomic island 2, encoding functions required for lipopolysaccharide biosynthesis, as well as inactivation of genes encoding urease, nutrient uptake and utilization, and outer membrane proteins may be factors contributing to the avirulence of B. ovis for humans. A 26.5 kb region of B. ovis ATCC25840 Chromosome II was absent from all the sequenced human pathogenic Brucella genomes, but was present in all of 17 B. ovis isolates tested and in three B. ceti isolates, suggesting that this DNA region may be of use for differentiating B. ovis from other Brucella spp. This is the first genomic analysis of a non-zoonotic Brucella species. The results suggest that inactivation of genes involved in nutrient acquisition and utilization, cell envelope structure and urease may have played a role in narrowing of the tissue tropism and host range of B. ovis.
doi:10.1371/journal.pone.0005519
PMCID: PMC2677664  PMID: 19436743
23.  A splice site mutation in hERG leads to cryptic splicing in human long QT syndrome 
Mutations in the human ether-a-go-go-related gene (hERG) cause type 2 long QT syndrome. In this study, we investigated the mechanism of the hERG splice site mutation 2398+1G>C and the genotype-phenotype relationship of mutation carriers in three unrelated kindreds with long QT syndrome. The effect of 2398+1G>C on mRNA splicing was studied by analysis of RNA isolated from lymphocytes of index patients and using minigenes expressed in HEK293 cells and neonatal rat ventricular myocytes. RT-PCR analysis revealed that the 2398+1G>C mutation disrupted the normal splicing and activated a cryptic splice donor site in intron 9, leading to the inclusion of 54 nt of the intron 9 sequence in hERG mRNA. The cryptic splicing resulted in an in-frame insertion of 18 amino acids in the middle of the cyclic nucleotide binding domain. In patch clamp experiments the splice mutant did not generate hERG current. Western blot and immunostaining studies showed that the mutant expressed an immature form of hERG protein that failed to reach the plasma membrane. Coexpression of the mutant and wild-type channels led to a dominant negative suppression of wild-type channel function by intracellular retention of heteromeric channels. Our results demonstrate that 2398+1G>C activates a cryptic site and generates a full-length hERG protein with an insertion of 18 amino acids, which leads to a trafficking defect of the mutant channel.
doi:10.1016/j.yjmcc.2008.01.002
PMCID: PMC2346779  PMID: 18272172
long QT syndrome; splicing mutation; arrhythmia; sudden death; myocytes
24.  Progesterone after previous preterm birth for prevention of neonatal respiratory distress syndrome (PROGRESS): a randomised controlled trial 
Background
Neonatal respiratory distress syndrome, as a consequence of preterm birth, is a major cause of early mortality and morbidity during infancy and childhood. Survivors of preterm birth continue to remain at considerable risk of both chronic lung disease and long-term neurological handicap. Progesterone is involved in the maintenance of uterine quiescence through modulation of the calcium-calmodulin-myosin-light-chain-kinase system in smooth muscle cells. The withdrawal of progesterone, either actual or functional is thought to be an antecedent to the onset of labour. While there have been recent reports of progesterone supplementation for women at risk of preterm birth which show promise in this intervention, there is currently insufficient data on clinically important outcomes for both women and infants to enable informed clinical decision-making.
The aims of this randomised, double blind, placebo controlled trial are to assess whether the use of vaginal progesterone pessaries in women with a history of previous spontaneous preterm birth will reduce the risk and severity of respiratory distress syndrome, so improving their infant's health, without increasing maternal risks.
Methods
Design: Multicentred randomised, double blind, placebo-controlled trial.
Inclusion Criteria: pregnant women with a live fetus, and a history of prior preterm birth at less than 37 weeks gestation and greater than 20 weeks gestation in the immediately preceding pregnancy, where onset of labour occurred spontaneously, or in association with cervical incompetence, or following preterm prelabour ruptured membranes.
Trial Entry & Randomisation: After obtaining written informed consent, eligible women will be randomised between 18 and 23+6 weeks gestation using a central telephone randomisation service. The randomisation schedule prepared by non clinical research staff will use balanced variable blocks, with stratification according to plurality of the pregnancy and centre where planned to give birth. Eligible women will be randomised to either vaginal progesterone or vaginal placebo.
Study Medication & Treatment Schedules: Treatment packs will appear identical. Woman, caregivers and research staff will be blinded to treatment allocation.
Primary Study Outcome: Neonatal Respiratory Distress Syndrome (defined by incidence and severity).
Sample Size: of 984 women to show a 40% reduction in respiratory distress syndrome from 15% to 9% (p = 0.05, 80% power).
Discussion
This is a protocol for a randomised trial.
Clinical Trial Registration
Current Controlled Trials ISRCTN20269066
doi:10.1186/1471-2393-9-6
PMCID: PMC2653463  PMID: 19239712
25.  Integral and peripheral association of proteins and protein complexes with Yersinia pestis inner and outer membranes 
Proteome Science  2009;7:5.
Yersinia pestis proteins were sequentially extracted from crude membranes with a high salt buffer (2.5 M NaBr), an alkaline solution (180 mM Na2CO3, pH 11.3) and membrane denaturants (8 M urea, 2 M thiourea and 1% amidosulfobetaine-14). Separation of proteins by 2D gel electrophoresis was followed by identification of more than 600 gene products by MS. Data from differential 2D gel display experiments, comparing protein abundances in cytoplasmic, periplasmic and all three membrane fractions, were used to assign proteins found in the membrane fractions to three protein categories: (i) integral membrane proteins and peripheral membrane proteins with low solubility in aqueous solutions (220 entries); (ii) peripheral membrane proteins with moderate to high solubility in aqueous solutions (127 entries); (iii) cytoplasmic or ribosomal membrane-contaminating proteins (80 entries). Thirty-one proteins were experimentally associated with the outer membrane (OM). Circa 50 proteins thought to be part of membrane-localized, multi-subunit complexes were identified in high Mr fractions of membrane extracts via size exclusion chromatography. This data supported biologically meaningful assignments of many proteins to the membrane periphery. Since only 32 inner membrane (IM) proteins with two or more predicted transmembrane domains (TMDs) were profiled in 2D gels, we resorted to a proteomic analysis by 2D-LC-MS/MS. Ninety-four additional IM proteins with two or more TMDs were identified. The total number of proteins associated with Y. pestis membranes increased to 456 and included representatives of all six β-barrel OM protein families and 25 distinct IM transporter families.
doi:10.1186/1477-5956-7-5
PMCID: PMC2663777  PMID: 19228400

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