B.C. Women's Hospital & Health Centre

BACKGROUND: Postpartum hemorrhage (PPH) is a major cause of maternal mortality and morbidity worldwide. Several recent publications have noted an increasing trend in incidence over time. The international PPH collaboration was convened to explore the observed trends and to set out actions to address the factors identified. METHODS: We reviewed available data sources on the incidence of PPH over time in Australia, Belgium, Canada, France, the United Kingdom and the USA. Where information was available, the incidence of PPH was stratified by cause. RESULTS: We observed an increasing trend in PPH, using heterogeneous definitions, in Australia, Canada, the UK and the USA. The observed increase in PPH in Australia, Canada and the USA was limited solely to immediate/atonic PPH. We noted increasing rates of severe adverse outcomes due to hemorrhage in Australia, Canada, the UK and the USA. CONCLUSION: Key Recommendations 1. Future revisions of the International Classification of Diseases should include separate codes for atonic PPH and PPH immediately following childbirth that is due to other causes. Also, additional codes are required for placenta accreta/percreta/increta. 2. Definitions of PPH should be unified; further research is required to investigate how definitions are applied in practice to the coding of data. 3. Additional improvement in the collection of data concerning PPH is required, specifically including a measure of severity. 4. Further research is required to determine whether an increased rate of reported PPH is also observed in other countries, and to further investigate potential risk factors including increased duration of labor, obesity and changes in second and third stage management practice. 5. Training should be provided to all staff involved in maternity care concerning assessment of blood loss and the monitoring of women after childbirth. This is key to reducing the severity of PPH and preventing any adverse outcomes. 6. Clinicians should be more vigilant given the possibility that the frequency and severity of PPH has in fact increased. This applies particularly to small hospitals with relatively few deliveries where management protocols may not be defined adequately and drugs or equipment may not be on hand to deal with unexpected severe PPH.

BACKGROUND: The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear. METHODS: We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational hypertension, office diastolic blood pressure of 90 to 105 mm Hg (or 85 to 105 mm Hg if the woman was taking antihypertensive medications), and a live fetus. Women were randomly assigned to less-tight control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days. The secondary outcome was serious maternal complications occurring up to 6 weeks post partum or until hospital discharge, whichever was later. RESULTS: Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-outcome rates were similar among 493 women assigned to less-tight control and 488 women assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7% and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4). Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-control group and 27.5% of the women in the tight-control group (P<0.001). CONCLUSIONS: We found no significant between-group differences in the risk of pregnancy loss, high-level neonatal care, or overall maternal complications, although less-tight control was associated with a significantly higher frequency of severe maternal hypertension. (Funded by the Canadian Institutes of Health Research; CHIPS Current Controlled Trials number, ISRCTN71416914; ClinicalTrials.gov number, NCT01192412.).

BACKGROUND: Endometriosis, defined as the presence of ectopic endometrial stroma and epithelium, affects approximately 10% of reproductive-age women and can cause pelvic pain and infertility. Endometriotic lesions are considered to be benign inflammatory lesions but have cancerlike features such as local invasion and resistance to apoptosis. METHODS: We analyzed deeply infiltrating endometriotic lesions from 27 patients by means of exomewide sequencing (24 patients) or cancer-driver targeted sequencing (3 patients). Mutations were validated with the use of digital genomic methods in microdissected epithelium and stroma. Epithelial and stromal components of lesions from an additional 12 patients were analyzed by means of a droplet digital polymerase-chain-reaction (PCR) assay for recurrent activating KRAS mutations. RESULTS: Exome sequencing revealed somatic mutations in 19 of 24 patients (79%). Five patients harbored known cancer driver mutations in ARID1A, PIK3CA, KRAS, or PPP2R1A, which were validated by Safe-Sequencing System or immunohistochemical analysis. The likelihood of driver genes being affected at this rate in the absence of selection was estimated at P=0.001 (binomial test). Targeted sequencing and a droplet digital PCR assay identified KRAS mutations in 2 of 3 patients and 3 of 12 patients, respectively, with mutations in the epithelium but not the stroma. One patient harbored two different KRAS mutations, c.35G→T and c.35G→C, and another carried identical KRAS c.35G→A mutations in three distinct lesions. CONCLUSIONS: We found that lesions in deep infiltrating endometriosis, which are associated with virtually no risk of malignant transformation, harbor somatic cancer driver mutations. Ten of 39 deep infiltrating lesions (26%) carried driver mutations; all the tested somatic mutations appeared to be confined to the epithelial compartment of endometriotic lesions.

BACKGROUND: Screening for aneuploid pregnancies is routinely performed after 15 weeks of gestation and has a sensitivity of approximately 65 percent, with a false positive rate of 5 percent. First-trimester markers of aneuploidy have been developed, but their use in combination has not been adequately evaluated in clinical practice. METHODS: We conducted a multicenter study of screening for trisomies 21 and 18 among patients with pregnancies between 74 and 97 days of gestation, based on maternal age, maternal levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A, and ultrasonographic measurement of fetal nuchal translucency. A screening result was considered to be positive for trisomy 21 if the calculated risk was at least 1 in 270 pregnancies and positive for trisomy 18 if the risk was at least 1 in 150. RESULTS: Screening was completed in 8514 patients with singleton pregnancies. This approach to screening identified 85.2 percent of the 61 cases of Down's syndrome (95 percent confidence interval, 73.8 to 93.0), with a false positive rate of 9.4 percent (95 percent confidence interval, 8.8 to 10.1). At a false positive rate of 5 percent, the detection rate was 78.7 percent (95 percent confidence interval, 66.3 to 88.1). Screening identified 90.9 percent of the 11 cases of trisomy 18 (95 percent confidence interval, 58.7 to 99.8), with a 2 percent false positive rate. Among women 35 years of age or older, screening identified 89.8 percent of fetuses with trisomy 21, with a false positive rate of 15.2 percent, and 100 percent of fetuses with trisomy 18. CONCLUSIONS: First-trimester screening for trisomies 21 and 18 on the basis of maternal age, maternal levels of free beta human chorionic gonadotropin and pregnancy-associated plasma protein A, and measurement of fetal nuchal translucency has good sensitivity at an acceptable false positive rate.

BACKGROUND: Stillbirths are a major public health issue and a sensitive marker of the quality of care around pregnancy and birth. The UN Global Strategy for Women's, Children's and Adolescents' Health (2016-30) and the Every Newborn Action Plan (led by UNICEF and WHO) call for an end to preventable stillbirths. A first step to prevent stillbirths is obtaining standardised measurement of stillbirth rates across countries. We estimated stillbirth rates and their trends for 195 countries from 2000 to 2019 and assessed progress over time. METHODS: For a systematic assessment, we created a dataset of 2833 country-year datapoints from 171 countries relevant to stillbirth rates, including data from registration and health information systems, household-based surveys, and population-based studies. After data quality assessment and exclusions, we used 1531 datapoints to estimate country-specific stillbirth rates for 195 countries from 2000 to 2019 using a Bayesian hierarchical temporal sparse regression model, according to a definition of stillbirth of at least 28 weeks' gestational age. Our model combined covariates with a temporal smoothing process such that estimates were informed by data for country-periods with high quality data, while being based on covariates for country-periods with little or no data on stillbirth rates. Bias and additional uncertainty associated with observations based on alternative stillbirth definitions and source types, and observations that were subject to non-sampling errors, were included in the model. We compared the estimated stillbirth rates and trends to previously reported mortality estimates in children younger than 5 years. FINDINGS: Globally in 2019, an estimated 2·0 million babies (90% uncertainty interval [UI] 1·9-2·2) were stillborn at 28 weeks or more of gestation, with a global stillbirth rate of 13·9 stillbirths (90% UI 13·5-15·4) per 1000 total births. Stillbirth rates in 2019 varied widely across regions, from 22·8 stillbirths (19·8-27·7) per 1000 total births in west and central Africa to 2·9 (2·7-3·0) in western Europe. After west and central Africa, eastern and southern Africa and south Asia had the second and third highest stillbirth rates in 2019. The global annual rate of reduction in stillbirth rate was estimated at 2·3% (90% UI 1·7-2·7) from 2000 to 2019, which was lower than the 2·9% (2·5-3·2) annual rate of reduction in neonatal mortality rate (for neonates aged <28 days) and the 4·3% (3·8-4·7) annual rate of reduction in mortality rate among children aged 1-59 months during the same period. Based on the lower bound of the 90% UIs, 114 countries had an estimated decrease in stillbirth rate since 2000, with four countries having a decrease of at least 50·0%, 28 having a decrease of 25·0-49·9%, 50 having a decrease of 10·0-24·9%, and 32 having a decrease of less than 10·0%. For the remaining 81 countries, we found no decrease in stillbirth rate since 2000. Of these countries, 34 were in sub-Saharan Africa, 16 were in east Asia and the Pacific, and 15 were in Latin America and the Caribbean. INTERPRETATION: Progress in reducing the rate of stillbirths has been slow compared with decreases in the mortality rate of children younger than 5 years. Accelerated improvements are most needed in the regions and countries with high stillbirth rates, particularly in sub-Saharan Africa. Future prevention of stillbirths needs increased efforts to raise public awareness, improve data collection, assess progress, and understand public health priorities locally, all of which require investment. FUNDING: Bill & Melinda Gates Foundation and the UK Foreign, Commonwealth and Development Office.

OBJECTIVE: To review outcomes in randomised controlled trials comparing hydralazine against other antihypertensives for severe hypertension in pregnancy. STUDY DESIGN: Meta-analysis of randomised controlled trials (published between 1966 and September 2002) of short acting antihypertensives for severe hypertension in pregnancy. Independent data abstraction by two reviewers. Data were entered into RevMan software for analysis (fixed effects model, relative risk and 95% confidence interval); in a secondary analysis, risk difference was also calculated. RESULTS: Of 21 trials (893 women), eight compared hydralazine with nifedipine and five with labetalol. Hydralazine was associated with a trend towards less persistent severe hypertension than labetalol (relative risk 0.29 (95% confidence interval 0.08 to 1.04); two trials), but more severe hypertension than nifedipine or isradipine (1.41 (0.95 to 2.09); four trials); there was significant heterogeneity in outcome between trials and differences in methodological quality. Hydralazine was associated with more maternal hypotension (3.29 (1.50 to 7.23); 13 trials); more caesarean sections (1.30 (1.08 to 1.59); 14 trials); more placental abruption (4.17 (1.19 to 14.28); five trials); more maternal oliguria (4.00 (1.22 to 12.50); three trials); more adverse effects on fetal heart rate (2.04 (1.32 to 3.16); 12 trials); and more low Apgar scores at one minute (2.70 (1.27 to 5.88); three trials). For all but Apgar scores, analysis by risk difference showed heterogeneity between trials. Hydralazine was associated with more maternal side effects (1.50 (1.16 to 1.94); 12 trials) and with less neonatal bradycardia than labetalol (risk difference -0.24 (-0.42 to -0.06); three trials). CONCLUSIONS: The results are not robust enough to guide clinical practice, but they do not support use of hydralazine as first line for treatment of severe hypertension in pregnancy. Adequately powered clinical trials are needed, with a comparison of labetalol and nifedipine showing the most promise.

UNLABELLED: Congenital cystic adenomatoid malformation of the lung (CCAM) is diagnosed by prenatal ultrasonography with an increasing frequency but controversy persists as to its prognosis and prenatal management. METHOD: A multi-institutional study of cases of CCAM diagnosed antenatally identified by ultrasonographers and by a review of hospital charts. RESULTS: We obtained 48 cases from five centers. We estimate the incidence of CCAM at 1:25,000 to 1:35,000 pregnancies. The incidence of voluntary abortions was 15% (7/48), of spontaneous abortions 2% (1/41) and of postnatal death 10% (4/40). One of the postnatal deaths was from trisomy 18. Of the 7 aborted fetuses, 2 had multiple malformations and 1 had severe hydrops and oligohydramnios; the other 4 had a large mass with mediastinal displacement but without hydrops. When pregnancy was allowed to continue, 56% of the lesions regressed spontaneously, even though one third of these had initial progression. In 17 cases (42%) the mediastinal shift corrected itself, sometimes by simple growth of the fetus but most often by a decrease in the size of the lung mass. In 1 fetus, repeated needle decompressions followed by double-pigtail catheter drainage of large cysts allowed regression of hydrops. Despite this, neonatal death occurred from pulmonary hypoplasia. CONCLUSION: CCAM can lead to fetal or neonatal demise from hydrops, lung hypoplasia, prematurity or severe associated malformations, but has a good prognosis in the majority of cases.

OBJECTIVE: To estimate the incidence of anemia in pregnancy and compare the maternal and perinatal outcomes of women with and without anemia. METHODS: We conducted a population-based retrospective cohort study on all pregnant women in British Columbia who had a live birth or stillbirth at or after 20 weeks of gestation between 2004 and 2016. Women were diagnosed with anemia based on two criteria: third-trimester hemoglobin value or a delivery admission diagnosis of anemia (made before delivery). Anemia was categorized into no anemia (hemoglobin 11 g/dL or greater), mild (9-10.9 g/dL), moderate (7-8.9 g/dL), severe (less than 7 g/dL), or anemia of unspecified severity (with diagnosis made before delivery). Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% CIs expressing the association between anemia and maternal and perinatal outcomes. RESULTS: Of 515,270 women in the study population, 65,906 (12.8%) had anemia: 11.8%, 0.43%, and 0.02% had mild, moderate, and severe anemia, respectively, and 0.58% had anemia of unspecified severity. Anemic women had longer hospitalization duration and more antenatal admissions, and rates of preeclampsia, placenta previa and cesarean delivery were higher among women with anemia. The intrapartum-postpartum blood transfusion rate was 5.1 per 1,000 among women without anemia, and higher among women with anemia (aOR 2.45, 95% CI 1.74-3.45 for mild anemia; 21.3, 95% CI 12.2-37.3 for moderate anemia; not analyzable for severe anemia; and 48.3, 95% CI 6.60-353.9 for anemia of unspecified severity). Anemia was associated with preterm birth (mild anemia, aOR 1.09, 95% CI 1.05-1.12; moderate anemia, aOR 2.26, 95% CI 2.02-2.54; anemia of unspecified severity, aOR 2.27, 95% CI 2.06-2.50), small-for-gestational-age live birth, low 5-minute Apgar score, neonatal death, and perinatal death. CONCLUSION: Maternal anemia in pregnancy represents a common and potentially reversible risk factor associated with antepartum, intrapartum, and postpartum maternal morbidity and perinatal morbidity and mortality.

BACKGROUND: Coronary heart disease (CHD) is the single most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people live with CHD and may need support to manage their symptoms and improve prognosis. Cardiac rehabilitation is a complex multifaceted intervention which aims to improve the health outcomes of people with CHD. Cardiac rehabilitation consists of three core modalities: education, exercise training and psychological support. This is an update of a Cochrane systematic review previously published in 2011, which aims to investigate the specific impact of the educational component of cardiac rehabilitation. OBJECTIVES: 1. To assess the effects of patient education delivered as part of cardiac rehabilitation, compared with usual care on mortality, morbidity, health-related quality of life (HRQoL) and healthcare costs in patients with CHD.2. To explore the potential study level predictors of the effects of patient education in patients with CHD (e.g. individual versus group intervention, timing with respect to index cardiac event). SEARCH METHODS: We updated searches from the previous Cochrane review, by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library, Issue 6, 2016), MEDLINE (Ovid), Embase (Ovid), PsycINFO (Ovid) and CINAHL (EBSCO) in June 2016. Three trials registries, previous systematic reviews and reference lists of included studies were also searched. No language restrictions were applied. SELECTION CRITERIA: 1. Randomised controlled trials (RCTs) where the primary interventional intent was education delivered as part of cardiac rehabilitation.2. Studies with a minimum of six-months follow-up and published in 1990 or later.3. Adults with a diagnosis of CHD. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all identified references for inclusion based on the above inclusion criteria. One author extracted study characteristics from the included trials and assessed their risk of bias; a second review author checked data. Two independent reviewers extracted outcome data onto a standardised collection form. For dichotomous variables, risk ratios and 95% confidence intervals (CI) were derived for each outcome. Heterogeneity amongst included studies was explored qualitatively and quantitatively. Where appropriate and possible, results from included studies were combined for each outcome to give an overall estimate of treatment effect. Given the degree of clinical heterogeneity seen in participant selection, interventions and comparators across studies, we decided it was appropriate to pool studies using random-effects modelling. We planned to undertake subgroup analysis and stratified meta-analysis, sensitivity analysis and meta-regression to examine potential treatment effect modifiers. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the quality of the evidence and the GRADE profiler (GRADEpro GDT) to create summary of findings tables. MAIN RESULTS: This updated review included a total of 22 trials which randomised 76,864 people with CHD to an education intervention or a 'no education' comparator. Nine new trials (8215 people) were included for this update. We judged most included studies as low risk of bias across most domains. Educational 'dose' ranged from one 40 minute face-to-face session plus a 15 minute follow-up call, to a four-week residential stay with 11 months of follow-up sessions. Control groups received usual medical care, typically consisting of referral to an outpatient cardiologist, primary care physician, or both.We found evidence of no difference in effect of education-based interventions on total mortality (13 studies, 10,075 participants; 189/5187 (3.6%) versus 222/4888 (4.6%); random effects risk ratio (RR) 0.80, 95% CI 0.60 to 1.05; moderate quality evidence). Individual causes of mortality were reported rarely, and we were unable to report separate results for cardiovascular mortality or non-cardiovascular mortality. There was evidence of no difference in effect of education-based interventions on fatal and/or non fatal myocardial infarction (MI) (2 studies, 209 participants; 7/107 (6.5%) versus 12/102 (11.8%); random effects RR 0.63, 95% CI 0.26 to 1.48; very low quality of evidence). However, there was some evidence of a reduction with education in fatal and/or non-fatal cardiovascular events (2 studies, 310 studies; 21/152 (13.8%) versus 61/158 (38.6%); random effects RR 0.36, 95% CI 0.23 to 0.56; low quality evidence). There was evidence of no difference in effect of education on the rate of total revascularisations (3 studies, 456 participants; 5/228 (2.2%) versus 8/228 (3.5%); random effects RR 0.58, 95% CI 0.19 to 1.71; very low quality evidence) or hospitalisations (5 studies, 14,849 participants; 656/10048 (6.5%) versus 381/4801 (7.9%); random effects RR 0.93, 95% CI 0.71 to 1.21; very low quality evidence). There was evidence of no difference between groups for all cause withdrawal (17 studies, 10,972 participants; 525/5632 (9.3%) versus 493/5340 (9.2%); random effects RR 1.04, 95% CI 0.88 to 1.22; low quality evidence). Although some health-related quality of life (HRQoL) domain scores were higher with education, there was no consistent evidence of superiority across all domains. AUTHORS' CONCLUSIONS: We found no reduction in total mortality, in people who received education delivered as part of cardiac rehabilitation, compared to people in control groups (moderate quality evidence). There were no improvements in fatal or non fatal MI, total revascularisations or hospitalisations, with education. There was some evidence of a reduction in fatal and/or non-fatal cardiovascular events with education, but this was based on only two studies. There was also some evidence to suggest that education-based interventions may improve HRQoL. Our findings are supportive of current national and international clinical guidelines that cardiac rehabilitation for people with CHD should be comprehensive and include educational interventions together with exercise and psychological therapy. Further definitive research into education interventions for people with CHD is needed.

BACKGROUND: Although intravenous glycoprotein IIb/IIIa inhibitors are beneficial in patients with acute coronary syndromes, prolonged oral IIb/IIIa inhibition might provide an additional reduction in recurrent events. METHODS AND RESULTS: Investigators at 888 hospitals in 29 countries enrolled 10 288 patients with acute coronary syndromes, which was defined as ischemic pain at rest within 72 hours of randomization, associated with positive cardiac markers, electrocardiographic changes, or prior cardiovascular disease. Patients received aspirin and were randomized to receive, for the duration of the trial, (1) 50 mg of orbofiban twice daily (50/50 group), (2) 50 mg of orbofiban twice daily for 30 days followed by 30 mg of orbofiban twice daily (50/30 group), or (3) a placebo. The primary composite end point was death, myocardial infarction, recurrent ischemia requiring rehospitalization, urgent revascularization, or stroke. The trial was terminated prematurely because of an unexpected increase in 30-day mortality in the 50/30 orbofiban group. Mortality through 10 months was 3.7% for the placebo group versus 5.1% in the 50/30 group (P=0.008) and 4.5% in the 50/50 group (P=0.11). There were no differences in the primary end point (22.9%, 23.1%, and 22.8%, for the placebo, 50/30, and 50/50 groups, respectively). Major or severe bleeding (but not intracranial hemorrhage) was higher with orbofiban; it occurred in 2. 0%, 3.7% (P=0.0004), and 4.5% (P<0.0001) of patients, respectively. Exploratory subgroup analyses found that patients who underwent percutaneous coronary intervention had a lower mortality and a significant reduction in the composite end point (P=0.001) with orbofiban. CONCLUSIONS: -Fixed-dose orbofiban failed to reduce major cardiovascular events and was associated with increased mortality in this broad population of patients with acute coronary syndromes; however, a benefit was observed among patients who underwent percutaneous coronary intervention.

The purposeful application of fermentation in food and beverage preparation, as a means to provide palatability, nutritional value, preservative, and medicinal properties, is an ancient practice. Fermented foods and beverages continue to make a significant contribution to the overall patterns of traditional dietary practices. As our knowledge of the human microbiome increases, including its connection to mental health (for example, anxiety and depression), it is becoming increasingly clear that there are untold connections between our resident microbes and many aspects of physiology. Of relevance to this research are new findings concerning the ways in which fermentation alters dietary items pre-consumption, and in turn, the ways in which fermentation-enriched chemicals (for example, lactoferrin, bioactive peptides) and newly formed phytochemicals (for example, unique flavonoids) may act upon our own intestinal microbiota profile. Here, we argue that the consumption of fermented foods may be particularly relevant to the emerging research linking traditional dietary practices and positive mental health. The extent to which traditional dietary items may mitigate inflammation and oxidative stress may be controlled, at least to some degree, by microbiota. It is our contention that properly controlled fermentation may often amplify the specific nutrient and phytochemical content of foods, the ultimate value of which may associated with mental health; furthermore, we also argue that the microbes (for example, Lactobacillus and Bifidobacteria species) associated with fermented foods may also influence brain health via direct and indirect pathways.

BACKGROUND: Although hysteroscopy is frequently used in the management of subfertile women, a systematic review of the evidence on this subject is lacking. METHODS: We summarized and appraised the evidence for the benefit yielded by this procedure. Our systematic search was limited to randomized and controlled studies. The QUOROM and MOOSE guidelines were followed. Language restrictions were not applied. RESULTS: We identified 30 relevant publications. Hysteroscopic removal of endometrial polyps with a mean diameter of 16 mm detected by ultrasound doubles the pregnancy rate when compared with diagnostic hysteroscopy and polyp biopsy in patients undergoing intrauterine insemination, starting 3 months after the surgical intervention [relative risk (RR) = 2.3; 95% confidence interval (CI): 1.6-3.2]. In patients with one fibroid structure smaller than 4 cm, there was a marginally significant benefit from myomectomy when compared with expectant management (RR = 1.9; 95% CI: 1.0-3.7). Hysteroscopic metroplasty for septate uterus resulted in fewer pregnancies in patients with subfertility when compared with those with recurrent pregnancy loss (RR = 0.7; 95% CI: 0.5-0.9). Randomized controlled studies on hysteroscopic treatment of intrauterine adhesions are lacking. Hysteroscopy in the cycle preceding a subsequent IVF attempt nearly doubles the pregnancy rate in patients with at least two failed IVF attempts compared with starting IVF immediately (RR = 1.7; 95% CI: 1.5-2.0). CONCLUSIONS: Scarce evidence on the effectiveness of hysteroscopic surgery in subfertile women with polyps, fibroids, septate uterus or intrauterine adhesions indicates a potential benefit. More randomized controlled trials are needed before widespread use of hysteroscopic surgery in the general subfertile population can be justified.

OBJECTIVES: Identify determinants of neurodevelopmental outcome in preterm children. METHODS: Prospective national cohort study of children born between 2009 and 2011 at <29 weeks gestational age, admitted to one of 28 Canadian neonatal intensive care units and assessed at a Canadian Neonatal Follow-up Network site at 21 months corrected age for cerebral palsy (CP), visual, hearing and developmental status using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Stepwise regression analyses evaluated the effect of (1) prenatal and neonatal characteristics, (2) admission severity of illness, (3) major neonatal morbidities, (4) neonatal neuroimaging abnormalities, and (5) site on neurodevelopmental impairment (NDI) (Bayley-III score < 85, any CP, visual or hearing impairment), significant neurodevelopmental impairment (sNDI) (Bayley-III < 70, severe CP, blind or hearing aided and sNDI or death. RESULTS: Of the 3700 admissions without severe congenital anomalies, 84% survived to discharge and of the 2340 admissions, 46% (IQR site variation 38%-51%) had a NDI, 17% (11%-23%) had a sNDI, 6.4% (3.1%-8.6%) had CP, 2.6% (2.5%-13.3%) had hearing aids or cochlear implants and 1.6% (0%-3.1%) had a bilateral visual impairment. Bayley-III composite scores of <70 for cognitive, language and motor domains were 3.3%, 10.9% and 6.7%, respectively. Gestational age, sex, outborn, illness severity, bronchopulmonary dysplasia, necrotising enterocolitis, late-onset sepsis, retinopathy of prematurity, abnormal neuroimaging and site were significantly associated with NDI or sNDI. Site variation ORs for NDI, sNDI and sNDI/death ranged from 0.3-4.3, 0.04-3.5 and 0.12-1.96, respectively. CONCLUSION: Most preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes.

The severity of congenital diaphragmatic hernia (CDH) can be estimated prenatally using observed-to-expected lung-head ratios (by ultrasound) and total fetal lung volumes (by magnetic resonance imaging), as well as fetal liver position.

Gender inequity is a pervasive global challenge to health equity. Health promotion, as a field, has paid only limited attention to gender inequity to date, but could be an active agent of change if gender equity became an explicit goal of health promotion research, policy and programmes. As an aspect of gendered health systems, health promotion interventions may maintain, exacerbate or reduce gender-related health inequities, depending upon the degree and quality of gender-responsiveness within the programme or policy. This article introduces a framework for gender-transformative health promotion that builds on understanding gender as a determinant of health and outlines a continuum of actions to address gender and health. Gender-transformative health promotion interventions could play a significant role in improving the lives of millions of girls and women worldwide. Gender-related principles of action are identified that extend the core principles of health promotion but reflect the significance of attending to gender in the development and use of evidence, engagement of stakeholders and selection of interventions. We illustrate the framework with examples from a range of women's health promotion activities, including cardiovascular disease prevention, tobacco control, and alcohol use. The literature suggests that gender-responsiveness will enhance the acceptance, relevance and effectiveness of health promotion interventions. By moving beyond responsiveness to transformation, gender-transformative health promotion could enhance both health and social outcomes for large numbers of women and men, girls and boys.

BACKGROUND: Bias in studies of preventive medications can occur when healthier patients are more likely to initiate and adhere to therapy than less healthy patients. We sought evidence of this bias by examining associations between statin exposure and various outcomes that should not be causally affected by statin exposure, such as workplace and motor vehicle accidents. METHODS AND RESULTS: We conducted a prospective cohort study of statin patients using data from British Columbia, Canada, a multiethnic society with a population of 4.3 million people. Study subjects were 141 086 patients who initiated statins for primary prevention. We examined the association between adherence and multiple outcomes such as accidents and screening procedures using multivariable-adjusted Cox proportional hazards models. The study population was 49% female and had an average age of 61 years. The results from our multivariable-adjusted models showed that more adherent patients were less likely to have accidents than less adherent patients. This effect was greatest for motor vehicle accidents (hazard ratio, 0.75; 95% confidence interval, 0.72 to 0.79) and workplace accidents (hazard ratio, 0.77; 95% confidence interval, 0.74 to 0.81). More adherent patients had a greater likelihood of using screening services (hazard ratio, 1.17; 95% confidence interval, 1.15 to 1.20) and a lower likelihood of developing other diseases likely to be unrelated to a biological affect of a statin (hazard ratio, 0.87; 95% confidence interval, 0.86 to 0.89). CONCLUSIONS: Our study contributes compelling evidence that patients who adhere to statins are systematically more health seeking than comparable patients who do not remain adherent. Caution is warranted when interpreting analyses that attribute surprising protective effects to preventive medications.

BACKGROUND: Antihypertensives, such as beta-blockers, are used for pregnancy hypertension in the belief these will improve outcome for mother and baby. OBJECTIVES: To assess whether oral beta-blockers are better than placebo, or no beta-blocker, and have advantages over other antihypertensives, for women with mild to moderate pregnancy hypertension. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (May 2002), MEDLINE (1966 to May 2002), bibliographies of retrieved papers and personal files. SELECTION CRITERIA: Trials comparing beta-blockers with placebo or no therapy, or other antihypertensives, for women with mild to moderate pregnancy hypertension. DATA COLLECTION AND ANALYSIS: We extracted the data independently and were not blinded to trial characteristics or outcomes. Whenever possible, we contacted authors for missing data. MAIN RESULTS: Twenty-nine trials (approximately 2500 women) are included. Thirteen trials (1480 women) compared beta-blockers with placebo/no beta blocker. Oral beta-blockers decrease the risk of severe hypertension (relative risk (RR) 0.37, 95% confidence interval (CI) 0.26 to 0.53; 11 trials, N = 1128 women) and the need for additional antihypertensives (RR 0.44, 95% CI 0.31 to 0.62; 7 trials, N = 856 women). There are insufficient data for conclusions about the effect on perinatal mortality or preterm birth. Beta-blockers seem to be associated with an increase in small-for-gestational-age (SGA) infants (RR 1.36, 95% CI 1.02 to 1.82; 12 trials; N = 1346 women). Maternal hospital admission may be decreased, neonatal bradycardia increased and respiratory distress syndrome decreased, but these outcomes are reported in only a small proportion of trials. In 13 trials (854 women), beta-blockers were compared with methyldopa. Beta-blockers appear to be no more effective and probably equally as safe. Single small trials have compared beta-blockers with hydralazine, nicardipine or isradipine. It is unusual for women to change drugs due to side effects. REVIEWER'S CONCLUSIONS: Improvement in control of maternal blood pressure with use of beta-blockers would be worthwhile only if it were reflected in substantive benefits for mother and/or baby, and none have been clearly demonstrated. The effect of beta-blockers on perinatal outcome is uncertain; the worrying trend to an increase in SGA infants is partly dependent on one small outlying trial. Large randomised trials are needed to determine whether antihypertensive therapy in general (rather than beta-blocker therapy specifically) results in greater benefit than risk, for treatment of mild-moderate pregnancy hypertension. If so, then it would be appropriate to consider which antihypertensive is best, and beta-blockers should be evaluated.

OBJECTIVE: To review the spot protein:creatinine ratio and albumin:creatinine ratio as diagnostic tests for significant proteinuria in hypertensive pregnant women. DESIGN: Systematic review. DATA SOURCES: Medline and Embase, the Cochrane Library, reference lists, and experts. Review methods Literature search (1980-2007) for articles of the spot protein:creatinine ratio or albumin:creatinine ratio in hypertensive pregnancy, with 24 hour proteinuria as the comparator. RESULTS: 13 studies concerned the spot protein:creatinine ratio (1214 women with primarily gestational hypertension). Nine studies reported sensitivity and specificity for eight cut-off points, median 24 mg/mmol (range 17-57 mg/mmol; 0.15-0.50 mg/mg). Laboratory assays were not well described. Diagnostic test characteristics were recalculated for a cut-off point of 30 mg/mmol. No significant heterogeneity in cut-off points was found between studies over a range of proteinuria. Pooled values gave a sensitivity of 83.6% (95% confidence interval 77.5% to 89.7%), specificity of 76.3% (72.6% to 80.0%), positive likelihood ratio of 3.53 (2.83 to 4.49), and negative likelihood ratio of 0.21 (0.13 to 0.31) (nine studies, 1003 women). Two studies of the spot albumin:creatinine ratio (225 women) found optimal cut-off points of 2 mg/mmol for proteinuria of 0.3 g/day or more and 27 mg/mmol for albuminuria. CONCLUSION: The spot protein:creatinine ratio is a reasonable "rule-out" test for detecting proteinuria of 0.3 g/day or more in hypertensive pregnancy. Information on use of the albumin:creatinine ratio in these women is insufficient.

Abstract A photoplethysmogram (PPG) contains a wealth of cardiovascular system information, and with the development of wearable technology, it has become the basic technique for evaluating cardiovascular health and detecting diseases. However, due to the varying environments in which wearable devices are used and, consequently, their varying susceptibility to noise interference, effective processing of PPG signals is challenging. Thus, the aim of this study was to determine the optimal filter and filter order to be used for PPG signal processing to make the systolic and diastolic waves more salient in the filtered PPG signal using the skewness quality index. Nine types of filters with 10 different orders were used to filter 219 (2.1s) short PPG signals. The signals were divided into three categories by PPG experts according to their noise levels: excellent, acceptable, or unfit. Results show that the Chebyshev II filter can improve the PPG signal quality more effectively than other types of filters and that the optimal order for the Chebyshev II filter is the 4 th order.

OBJECTIVE: To determine the impact of partner support in the treatment of mothers suffering from postpartum depression (PPD). METHOD: Patients underwent a comprehensive psychiatric assessment and were enrolled in the study only if they met the DSM-IV criteria for major depressive disorder with postpartum onset. Patients with PPD (n = 29) were assigned randomly to 2 treatment groups: group 1 (control group) consisted of patients only (n = 13), while group 2 (support group) consisted of patients (n = 16) and their partners. The patients in both groups were seen for 7 psychoeducational visits each. In group 2, partners participated in 4 of the 7 visits. Patients in both groups were administered a set of questionnaires that included the Edinburgh Postnatal Depression Scale (EPDS), the Kellner Symptom Questionnaire, the Dyadic Adjustment Scale (DAS), and the Parental Bonding Instrument (PBI). In addition, during visits 1 and 7, all patients underwent assessment using the Mini International Neuropsychiatric Instrument (MINI), section A (major depressive episode). The partners in both groups completed the DAS and the General Health Questionnaire (GHQ). RESULTS: Relative to the control-group patients, the support-group patients displayed a significant decrease in depressive symptoms and other psychiatric conditions. Relative to the support group, the general health of the partners in the control group deteriorated. CONCLUSION: Partner support has a measurable effect on women experiencing PPD.