Health economics-informed planning of psychiatric care: A primer and curriculum framework for psychiatrists.

OBJECTIVE: Contemporary medical education lacks a strong focus on health economics which guides major decisions in private and public health services. We briefly outline the rationale, guiding principles, main analytic methods, and a suggested framework for health economics education in psychiatry. CONCLUSIONS: Health economics aims to improve the efficiency of healthcare. Some analytic methods can be harnessed by psychiatrists to better plan clinical care. Health economic methods will also assist psychiatrists in translating their expertise and clinical priorities more effectively to policy-makers, governments, and private insurers motivated by economic reasoning.

The socioeconomic gradient in mortality from ovarian, cervical, and endometrial cancer in Australian women, 2001-2018: A population-based study.

BACKGROUND: Socio-economic (SE) status is closely linked to health status and the mechanisms of this association are complex. One important adverse effect of SE disadvantage is vulnerability to cancer and cancer is a major cause of morbidity and mortality in Australia. AIMS: We aimed to estimate the effect of SE status on mortality rates from ovarian, cervical, and endometrial cancer. MATERIALS AND METHODS: National mortality data were obtained from the Australian Bureau of Statistics (ABS) for the calendar years from 2001 to 2018, inclusive. Individual deaths were grouped by the ABS Index of Relative Socio-economic Advantage and Disadvantage. Population data were obtained to provided denominators allowing calculation of mortality rates (deaths per 100 000 women aged 30-79 years). Statistical analyses performed included tabulating point-estimates of mortality rates and their changes over time and modelling the trends of rates using maximum likelihood method. RESULTS: Age-standardised mortality rates for ovarian and cervical cancer fell over the study period but increased for endometrial cancer. There was clear evidence of a SE gradient in the mortality rate for all three cancers. This SE gradient increased over the study period for ovarian and cervical cancer but remained unchanged for endometrial cancer. CONCLUSIONS: Women at greater SE disadvantage have higher rates of death from the commonest gynaecological cancers and this gradient has not reduced over the last two decades. After the COVID-19 pandemic efforts must be redoubled to ensure that Australians already at risk of ill health do not face even greater risks because of their circumstances.

Evaluation of the Arabin cervical pessary for prevention of preterm birth in women with a twin pregnancy and short cervix (STOPPIT-2): An open-label randomised trial and updated meta-analysis.

BACKGROUND: Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix. METHODS AND FINDINGS: We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women [92.0%]) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio [aOR] 0.87 [95% CI 0.55-1.38], p = 0.54). The primary neonatal outcome-a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery-was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 [95% CI 0.54-1.36], p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 [95% CI 0.50-1.11], p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses. CONCLUSIONS: These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out. TRIAL REGISTRATION: ISRCTN Registry ISRCTN 02235181. ClinicalTrials.gov NCT02235181.

Opt-in or opt-out health-care communication? A cross-sectional study.

BACKGROUND: Patients need medication and medical condition-related information to better self-manage their health. Health-care professionals (HCPs) should be able to actively provide information outside of one-on-one consultations; however, patient consent may be required. OBJECTIVE: To investigate the Australian public's preferences, and factors that may influence their preferences, towards an opt-in versus an opt-out approach to health communication. DESIGN: A cross-sectional study using a structured questionnaire administered via Computer-Assisted Telephone Interviewing. SETTING AND PARTICIPANTS: Participants across Australia who were adults, English-speaking and had a long-term medical condition. MAIN OUTCOME MEASURES: Preferences for opt-in vs opt-out approach to receiving follow-up tailored information. RESULTS: A total of 8683 calls were made to achieve the required sample size of 589 completed surveys. Many (346/589; 58.7%) indicated that they were interested in receiving tailored, ongoing follow-up information from their HCP. Nearly half (n = 281; 47.7%) preferred an opt-in service and 293/589 (49.7%) an opt-out service for receiving follow-up information. Reasons for preferring an opt-in service were being in control of the information received (n = 254); able to make a decision that is best for them (n = 245); opt-in service would save time for HCPs (n = 217); they may not want or need the information (n = 240). Many (n = 255) felt that an opt-out service should be part of the normal duty of care of their HCP and believed (n = 267) that this approach would ensure that everyone has access to information. CONCLUSIONS: Respondents were interested in receiving tailored information outside of consultation times. However, preferences for an opt-in or opt-out approach were divided.

The connected patient project: moving towards a population-based primary health care research registry.

BACKGROUND: The NHS pledges to give all patients access to clinical research. In England, 32% of General Practices are research active and only 14% of patients engage in research. This project aimed to evaluate consent-for-contact and communication in primary care patients. METHODS: An explanatory mixed methods study of patients and staff within a single general practice. The study included all patients over the age of 18 years, and excluded those on the palliative care register and those unable to give informed consent. The questionnaire asked recipients to indicate their preferred contact method and data-sharing permissions with three organisations: NHS, Universities and Commercial Companies. Survey recipients and staff were invited to take part in a semi-structured interview. Interviews explored project acceptability, feasibility and reasoning behind choices made. Statistical data were triangulated with interview data. RESULTS: The target patient population was 4678, 24% (n = 1148) responded. Seven hundred and three gave permission for at least one of the organisations to contact them. Older people were more likely to respond than young people, (p < 0.001). There was a trend for more women than men to give permissions however, in the 70 years plus age group this was reversed. Short message service was the preferred method of communication (48% n = 330), but those aged 70 years and over, preferred letter (p = 0.001). Interviews suggested patients felt the project was primarily about improving communication and secondly access to research. Patients trusted the NHS and university researchers. Staff interviewees found the project was less onerous than expected. Barriers to wider rollout included workload and the fragmented nature of NHS digital systems. CONCLUSIONS: A registry of patients was established; however, the response rate of 24% needs increasing before wider adoption. Health promotion and chronic disease-based research may recruit better when based in primary health care. Older demographics would be more likely to volunteer for research. NHS and academic researchers are trusted, commercial organisations less so. The move to digitalise communication methods has the potential to marginalise older women. Findings were used to drive forward two novel developments: a consent registry (Research+Me) and a federation-wide participant identification process.

Three perils of medico-political professional organisations: corporatisation, bureaucratisation and concentration of power.

OBJECTIVE: To discuss relevant factors affecting the effectiveness and membership engagement of medico-political professional organisations, for example, medical colleges, societies and associations. CONCLUSIONS: Medico-political professional organisations face perils from corporatisation, bureaucratisation and concentration of power that diminish membership engagement and influence. Actions to address these challenges are necessary to ensure the future viability of these organisations.

Universal third-trimester ultrasonic screening using fetal macrosomia in the prediction of adverse perinatal outcome: A systematic review and meta-analysis of diagnostic test accuracy.

BACKGROUND: The effectiveness of screening for macrosomia is not well established. One of the critical elements of an effective screening program is the diagnostic accuracy of a test at predicting the condition. The objective of this study is to investigate the diagnostic effectiveness of universal ultrasonic fetal biometry in predicting the delivery of a macrosomic infant, shoulder dystocia, and associated neonatal morbidity in low- and mixed-risk populations. METHODS AND FINDINGS: We conducted a predefined literature search in Medline, Excerpta Medica database (EMBASE), the Cochrane library and ClinicalTrials.gov from inception to May 2020. No language restrictions were applied. We included studies where the ultrasound was performed as part of universal screening and those that included low- and mixed-risk pregnancies and excluded studies confined to high risk pregnancies. We used the estimated fetal weight (EFW) (multiple formulas and thresholds) and the abdominal circumference (AC) to define suspected large for gestational age (LGA). Adverse perinatal outcomes included macrosomia (multiple thresholds), shoulder dystocia, and other markers of neonatal morbidity. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was carried out using the hierarchical summary receiver operating characteristic (ROC) and the bivariate logit-normal (Reitsma) models. We identified 41 studies that met our inclusion criteria involving 112,034 patients in total. These included 11 prospective cohort studies (N = 9986), one randomized controlled trial (RCT) (N = 367), and 29 retrospective cohort studies (N = 101,681). The quality of the studies was variable, and only three studies blinded the ultrasound findings to the clinicians. Both EFW >4,000 g (or 90th centile for the gestational age) and AC >36 cm (or 90th centile) had >50% sensitivity for predicting macrosomia (birthweight above 4,000 g or 90th centile) at birth with positive likelihood ratios (LRs) of 8.74 (95% confidence interval [CI] 6.84-11.17) and 7.56 (95% CI 5.85-9.77), respectively. There was significant heterogeneity at predicting macrosomia, which could reflect the different study designs, the characteristics of the included populations, and differences in the formulas used. An EFW >4,000 g (or 90th centile) had 22% sensitivity at predicting shoulder dystocia with a positive likelihood ratio of 2.12 (95% CI 1.34-3.35). There was insufficient data to analyze other markers of neonatal morbidity. CONCLUSIONS: In this study, we found that suspected LGA is strongly predictive of the risk of delivering a large infant in low- and mixed-risk populations. However, it is only weakly (albeit statistically significantly) predictive of the risk of shoulder dystocia. There was insufficient data to analyze other markers of neonatal morbidity.

Trends in metabolic surgery in reproductive-age women in Australia.

Obesity and polycystic ovary syndrome (PCOS) are common and have important reproductive consequences: 'metabolic surgery' - bariatric surgery and laparoscopic ovarian drilling (LOD) - have roles in their management. Using national data to determine age-stratified incidence rates of these procedures, we found that bariatric surgery is much more common than LOD. While the uptake of bariatric surgery is rapidly increasing, there has been a decline in the use of LOD in young women. It seems likely that other forms of care for PCOS-related anovulation resistant to clomiphene, such as the use of letrozole or in vitro fertilisation, are taking the place of LOD.

Socioeconomic status and uptake of reproductive carrier screening in Australia.

Reproductive carrier screening enables the early identification of genetic conditions that may impact the long-term health of a child, including cystic fibrosis, fragile X syndrome, and spinal muscular atrophy. We used unique data from the major providers of pathology services in Australia to profile women who intend on becoming, or who are, pregnant and access basic to advanced testing for genetic conditions. We found a strong socioeconomic gradient in the uptake of reproductive carrier screening, with women living in the most advantaged postcodes across Australia significantly being more likely to have reproductive carrier screening than those living in the most disadvantaged areas. These results highlight the need to minimise social and financial barriers that are currently limiting access.

"He looks gorgeous" - iuMR images and the transforming of foetal and parental identities.

The MERIDIAN study examined whether in-utero MRI (iuMRI) improves the accuracy of diagnosis of foetal brain abnormalities, when used as an adjunct to ultrasound anomaly scanning. A diagnostic iuMRI differs from routine ultrasound screening because of its infrequent use and scanning procedure. Nested within this trial, this sociological study explored the acceptability of iuMRI as a technology and its contribution to parental decision-making. Our sociological interpretation of the role of iuMR images in prenatal diagnosis draws on narrative interviews with women (and some partners) who underwent MRI imaging at three different centres. Overall, participants found iuMRI helpful in decision-making because it either confirmed or disconfirmed previous results, or provided additional information. Expectant couples experienced the iuMR imaging process as informative, but also as having emotive and practical value. Our paper extends the existing sociological literature on antenatal testing and visualising the foetus, by using iuMR diagnostic imaging to further explore the concept of the unborn entity. Our data suggest that alongside the iuMR images, the 'parental gaze' and accompanying commentary are used by parents to construct and transform foetal and parental identities despite ongoing uncertainties about, and shifting social contexts to their pregnancy.

Changes in the incidence and uptake of reproductive surgery versus in vitro fertilisation in Australia between 2001 and 2015: A population-based study.

OBJECTIVE: Improvements in success rates of assisted reproduction led to predictions that infertility surgery in both women and men would become extinct in developed countries. We sought to identify the changes in reproductive surgery that occurred between 2001 and 2015 to determine whether these predictions have been accurate. DESIGN: The Australian Institute of Health and Welfare (AIHW) national procedural dataset and the Australian Medicare Benefits Scheme (MBS) claims database were searched for procedure data for male and female reproductive surgery and assisted reproduction from January 2001 to December 2015. The denominators were based on annual point estimates of the total population aged 25-44 years (female) and 25-55 years (male) from the Australian Bureau of Statistics (ABS). This dataset provides procedures undertaken but not their indications. RESULTS: Over the study period the incidence of tubal surgery fell by 66%, vasectomy reversal by 33%, and surgical varicocoelectomy by 50%. In contrast, the rate of hysteroscopic myomectomy increased by 48%, hysteroscopic septoplasty by 125%, and laparoscopy for severe endometriosis increased by 84%. In vitro fertilisation oocyte retrievals increased by 90%. The rate of abdominal myomectomy was unchanged. CONCLUSION: Fertility surgery is not dead but has evolved.

Use of MRI in the diagnosis of fetal brain abnormalities in utero (MERIDIAN): a multicentre, prospective cohort study.

BACKGROUND: In-utero MRI (iuMRI) has shown promise as an adjunct to ultrasound but the comparative diagnostic performance has been poorly defined. We aimed to assess whether the diagnostic accuracy and confidence of the prenatal diagnosis of fetal brain abnormalities is improved with iuMRI and assess the clinical impact and patient acceptability of iuMRI. METHODS: We did a multicentre, prospective, cohort study in the UK, at 16 fetal medicine centres, of pregnant women aged 16 years or older whose fetus had a brain abnormality detected by ultrasound at a gestational age of 18 weeks or more, had no contraindications to iuMRI, and consented to enter the study. Women carrying a fetus suspected of having a brain anomaly on ultrasound had iuMRI done within 14 days of ultrasound. The findings were reviewed by two independent panels and used to estimate diagnostic accuracy and confidence by comparison with outcome diagnoses. Changes in diagnosis, prognosis, and clinical management brought about by iuMRI and patient acceptability were assessed. FINDINGS: Participants were recruited between July 29, 2011, and Aug 31, 2014. The cohort was subdivided by gestation into the 18 weeks to less than 24 weeks fetus cohort (n=369) and into the 24 weeks or older fetus cohort (n=201). Diagnostic accuracy was improved by 23% (95% CI 18-27) in the 18 weeks to less than 24 weeks group and 29% (23-36) in the 24 weeks and older group (p<0·0001 for both groups). The overall diagnostic accuracy was 68% for ultrasound and 93% for iuMRI (difference 25%, 95% CI 21-29). Dominant diagnoses were reported with high confidence on ultrasound in 465 (82%) of 570 cases compared with 544 (95%) of 570 cases on iuMRI. IuMRI provided additional diagnostic information in 387 (49%) of 783 cases, changed prognostic information in at least 157 (20%), and led to changes in clinical management in more than one in three cases. IuMRI also had high patient acceptability with at least 95% of women saying they would have an iuMRI study if a future pregnancy were complicated by a fetal brain abnormality. INTERPRETATION: iuMRI improves diagnostic accuracy and confidence for fetal brain anomalies and leads to management changes in a high proportion of cases. This finding, along with the high patient acceptability, leads us to propose that any fetus with a suspected brain abnormality on ultrasound should have iuMRI to better inform counselling and management decisions. FUNDING: National Institute for Health Research Health Technology Assessment programme.

Association between a national quality improvement program and excisional treatment of cervical dysplasia in Australia.

AIM: In Australia, the National Cervical Screening and HPV Vaccination Programs aim to reduce the incidence of cervical cancer. Identification and treatment of preinvasive disease is important, but excisional treatment has been associated with adverse pregnancy outcomes. A national quality improvement program (Cervical Quality Improvement Program [c-QuIP]) aimed to reduce the rate of excisional treatment in young human papilloma virus (HPV)-vaccinated women. This study examined national trends in the rate of excisional treatment in young women. METHODS: Comprehensive national data were obtained from Medicare Australia regarding incidence rates of excisional treatment for the 10-year period 2007 to 2016 inclusive. These data were used to calculate age-stratified incidence rates of excisional treatment in young (20-24 years), intermediate (25-34 years) and older (35-60 years) women. RESULTS: The rate of excisional treatment (procedures per 10 000 women) fell in young women (from 25 to 6/7, P < 0.005) and women of intermediate age (from 23 to 13, P < 0.005), but there was no significant change in the rate in women aged 35 to 60 years (from 7 to 6.5). CONCLUSION: In the decade since introduction of the National HPV Vaccination Program the rate of excisional treatment of the cervix in Australia has fallen in women aged less than 35 years but has not changed for older women. The introduction of a national program aiming to reduce the rate appeared to have little impact.

Hospital admission and surgical approach to tubal ectopic pregnancy in Australia 2000 to 2014: A population-based study.

BACKGROUND: There are several accepted approaches to management of ectopic pregnancy, both surgical and non-surgical. When a surgical approach is used, there appears to be an equipoise between tubal preservation and removal. We sought to determine the patterns of surgical management of ectopic pregnancy in Australia since the year 2000. MATERIALS AND METHODS: Data regarding hospital admissions for ectopic pregnancy were extracted from the Australian Institute of Health and Welfare national procedural dataset for the years 2000-2013. Surgical procedures were classified as open or laparoscopic, and involving salpingotomy or salpingectomy (tubal removal). The results were stratified into age bands. RESULTS: Over the study period hospital admission rates for ectopic pregnancy rose in women under the age of 30, without an increase in surgical procedures, while the rate of surgical procedures fell in women in older age groups. Rates of management of ectopic pregnancy via laparotomy fell in all age groups, as did rates of tubal preservation. CONCLUSION: Since the year 2000 there have been changes in the management of ectopic pregnancy, with significant reductions in open surgery and tubal preservation.

Maternal-choice caesarean section versus planned vaginal birth in low-risk primigravid women.

Rising rates of caesarean section (CS) have been attributed, in part, to maternal-choice CS (MCCS). There are few published data regarding maternal and perinatal risks comparing MCCS with planned vaginal birth (VB) in uncomplicated first pregnancies to inform choice. We report the results of a pragmatic patient-preference cohort study of private patients in Australia: 64 women planning MCCS and 113 women planning VB. There were few differences in outcome between the two groups. The study highlighted the well-recognised difficulties in undertaking prospective research into MCCS.

A randomised controlled trial of consumption of dark chocolate in pregnancy to reduce pre-eclampsia: Difficulties in recruitment, allocation and adherence.

In 2013-2014 we undertook a randomised controlled trial (RCT) to determine whether the daily ingestion of dark chocolate during pregnancy could reduce the incidence of pre-eclampsia in primigravidae. However, after two years we had not succeeded in recruiting more than 3.5% of the number of participants required to answer the research question, and the trial was halted. We also reviewed the literature on this topic and found it to be limited. We report here our findings and discuss the difficulties facing researchers in this area.

MRI for Fetal Developmental Brain Abnormalities: Perspectives From the Pregnant Patient.

Ultrasound is routinely used as a prenatal screening and diagnostic tool but has limitations. Some anomalies in the developing fetal brain can be difficult to detect, and in utero magnetic resonance imaging (iuMRI) is increasingly used as an adjunct to ultrasound. However, understandings of patient perspectives of iuMRI technology are still developing. Our qualitative study of 41 mothers who experienced iuMRI was embedded in a diagnostic accuracy trial and aimed to inform policy recommendations that might stem from the clinical findings. Our analysis suggests that iuMRI is seen as useful, offering valuable additional information and helping women make decisions about care options at a difficult time. However, patients' experiences demonstrated the uncertainty and anxiety associated with the prenatal diagnosis (PND) process relating to brain anomalies including the challenges of their embodied contributions. Our findings suggest more could be done to reduce the impact on pregnant women during an already difficult, anxious period.

Liver triacylglycerol content and gestational diabetes: effects of moderate energy restriction.

AIMS/HYPOTHESIS: Women with a history of gestational diabetes mellitus (GDM) have raised liver triacylglycerol. Restriction of energy intake in type 2 diabetes can normalise glucose control and liver triacylglycerol concentration but it is not known whether similar benefits could be achieved in GDM. The aim of this work was to examine liver triacylglycerol accumulation in women with GDM and the effect of modest energy restriction. METHODS: Sixteen women with GDM followed a 4 week diet (5 MJ [1200 kcal]/day). Liver triacylglycerol, before and after diet and postpartum, was measured by magnetic resonance. Insulin secretion and sensitivity were assessed before and after diet. Twenty-six women who underwent standard antenatal care for GDM (matched for age, BMI, parity and ethnicity) were used as a comparator group. RESULTS: Fourteen women, who completed the study, achieved a weight loss of 1.6 ± 1.7 kg over the 4 week dietary period. Mean weight change was -0.4 kg/week in the study group vs +0.3 kg/week in the comparator group (p = 0.002). Liver triacylglycerol level was normal but decreased following diet (3.7% [interquartile range, IQR 1.2-6.1%] vs 1.8% [IQR 0.7-3.1%], p = 0.004). There was no change in insulin sensitivity or production. Insulin was required in six comparator women vs none in the study group (eight vs two required metformin). Blood glucose control was similar for both groups. The hypo-energetic diet was well accepted. CONCLUSIONS/INTERPRETATION: Liver triacylglycerol in women with GDM was not elevated, unlike observations in non-pregnant women with a history of GDM. A 4 week hypo-energetic diet resulted in weight loss, reduced liver triacylglycerol and minimised pharmacotherapy. The underlying pathophysiology of glucose metabolism appeared unchanged.

Cell salvage and donor blood transfusion during cesarean section: A pragmatic, multicentre randomised controlled trial (SALVO).

BACKGROUND: Excessive haemorrhage at cesarean section requires donor (allogeneic) blood transfusion. Cell salvage may reduce this requirement. METHODS AND FINDINGS: We conducted a pragmatic randomised controlled trial (at 26 obstetric units; participants recruited from 4 June 2013 to 17 April 2016) of routine cell salvage use (intervention) versus current standard of care without routine salvage use (control) in cesarean section among women at risk of haemorrhage. Randomisation was stratified, using random permuted blocks of variable sizes. In an intention-to-treat analysis, we used multivariable models, adjusting for stratification variables and prognostic factors identified a priori, to compare rates of donor blood transfusion (primary outcome) and fetomaternal haemorrhage ≥2 ml in RhD-negative women with RhD-positive babies (a secondary outcome) between groups. Among 3,028 women randomised (2,990 analysed), 95.6% of 1,498 assigned to intervention had cell salvage deployed (50.8% had salvaged blood returned; mean 259.9 ml) versus 3.9% of 1,492 assigned to control. Donor blood transfusion rate was 3.5% in the control group versus 2.5% in the intervention group (adjusted odds ratio [OR] 0.65, 95% confidence interval [CI] 0.42 to 1.01, p = 0.056; adjusted risk difference -1.03, 95% CI -2.13 to 0.06). In a planned subgroup analysis, the transfusion rate was 4.6% in women assigned to control versus 3.0% in the intervention group among emergency cesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 2.2% versus 1.8% among elective cesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46). No case of amniotic fluid embolism was observed. The rate of fetomaternal haemorrhage was higher with the intervention (10.5% in the control group versus 25.6% in the intervention group, adjusted OR 5.63, 95% CI 1.43 to 22.14, p = 0.013). We are unable to comment on long-term antibody sensitisation effects. CONCLUSIONS: The overall reduction observed in donor blood transfusion associated with the routine use of cell salvage during cesarean section was not statistically significant. TRIAL REGISTRATION: This trial was prospectively registered on ISRCTN as trial number 66118656 and can be viewed on http://www.isrctn.com/ISRCTN66118656.

Vaginal progesterone prophylaxis for preterm birth (the OPPTIMUM study): a multicentre, randomised, double-blind trial.

BACKGROUND: Progesterone administration has been shown to reduce the risk of preterm birth and neonatal morbidity in women at high risk, but there is uncertainty about longer term effects on the child. METHODS: We did a double-blind, randomised, placebo-controlled trial of vaginal progesterone, 200 mg daily taken from 22-24 to 34 weeks of gestation, on pregnancy and infant outcomes in women at risk of preterm birth (because of previous spontaneous birth at ≤34 weeks and 0 days of gestation, or a cervical length ≤25 mm, or because of a positive fetal fibronectin test combined with other clinical risk factors for preterm birth [any one of a history in a previous pregnancy of preterm birth, second trimester loss, preterm premature fetal membrane rupture, or a history of a cervical procedure to treat abnormal smears]). The objective of the study was to determine whether vaginal progesterone prophylaxis given to reduce the risk of preterm birth affects neonatal and childhood outcomes. We defined three primary outcomes: fetal death or birth before 34 weeks and 0 days gestation (obstetric), a composite of death, brain injury, or bronchopulmonary dysplasia (neonatal), and a standardised cognitive score at 2 years of age (childhood), imputing values for deaths. Randomisation was done through a web portal, with participants, investigators, and others involved in giving the intervention, assessing outcomes, or analysing data masked to treatment allocation until the end of the study. Analysis was by intention to treat. This trial is registered at ISRCTN.com, number ISRCTN14568373. FINDINGS: Between Feb 2, 2009, and April 12, 2013, we randomly assigned 1228 women to the placebo group (n=610) and the progesterone group (n=618). In the placebo group, data from 597, 587, and 439 women or babies were available for analysis of obstetric, neonatal, and childhood outcomes, respectively; in the progesterone group the corresponding numbers were 600, 589, and 430. After correction for multiple outcomes, progesterone had no significant effect on the primary obstetric outcome (odds ratio adjusted for multiple comparisons [OR] 0·86, 95% CI 0·61-1·22) or neonatal outcome (OR 0·62, 0·38-1·03), nor on the childhood outcome (cognitive score, progesterone group vs placebo group, 97·3 [SD 17·9] vs 97·7 [17·5]; difference in means -0·48, 95% CI -2·77 to 1·81). Maternal or child serious adverse events were reported in 70 (11%) of 610 patients in the placebo group and 59 (10%) of 616 patients in the progesterone group (p=0·27). INTERPRETATION: Vaginal progesterone was not associated with reduced risk of preterm birth or composite neonatal adverse outcomes, and had no long-term benefit or harm on outcomes in children at 2 years of age. FUNDING: Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. The EME Programme is funded by the MRC and NIHR, with contributions from the Chief Scientist Office in Scotland and National Institute for Social Care and Research in Wales.