The relation of integrated psychological therapy to resting state functional brain connectivity networks in patients with schizophrenia.

Functional brain dysconnectivity measured with resting state functional magnetic resonance imaging (rsfMRI) has been linked to cognitive impairment in schizophrenia. This study investigated the effects on functional brain connectivity of Integrated Psychological Therapy (IPT), a cognitive behavioral oriented group intervention program, in 31 patients with schizophrenia. Patients received IPT or an equal intensity non-specific psychological treatment in a non-randomized design. Evidence of improvement in executive and social functions, psychopathology and overall level of functioning was observed after treatment completion at six months only in the IPT treatment group and was partially sustained at one-year follow up. Independent Component Analysis and Isometric Mapping (ISOMAP), a non-linear manifold learning algorithm, were used to construct functional connectivity networks from the rsfMRI data. Functional brain dysconnectivity was observed in patients compared to a group of 17 healthy controls, both globally and specifically including the default mode (DMN) and frontoparietal network (FPN). DMN and FPN connectivity were reversed towards healthy control patterns only in the IPT treatment group and these effects were sustained at follow up for DMN but not FPN. These data suggest the use of rsfMRI as a biomarker for accessing and monitoring the therapeutic effects of cognitive remediation therapy in schizophrenia.

Interim data monitoring in cluster randomised trials: Practical issues and a case study.

BACKGROUND: There is an abundance of guidance for the interim monitoring of individually randomised trials. While methodological literature exists on how to extend these methods to cluster randomised trials, there is little guidance on practical implementation. Cluster trials have many features which make their monitoring needs different. We outline the methodological and practical challenges of interim monitoring of cluster trials; and apply these considerations to a case study. CASE STUDY: The E-MOTIVE study is an 80-cluster randomised trial of a bundle of interventions to treat postpartum haemorrhage. The proposed data monitoring plan includes (1) monitor sample size assumptions, (2) monitor for evidence of selection bias, and (3) an interim assessment of the primary outcome, as well as monitoring data completeness. The timing of the sample size monitoring is chosen with both consideration of statistical precision and to allow time to recruit more clusters. Monitoring for selection bias involves comparing individual-level characteristics and numbers recruited between study arms to identify any post-randomisation participant identification bias. An interim analysis of outcomes presented with 99.9% confidence intervals using the Haybittle-Peto approach should mitigate any concern regarding the inflation of type-I error. The pragmatic nature of the trial means monitoring for adherence is not relevant, as it is built into a process evaluation. CONCLUSIONS: The interim analyses of cluster trials have a number of important differences to monitoring individually randomised trials. In cluster trials, there will often be a greater need to monitor nuisance parameters, yet there will often be considerable uncertainty in their estimation. This means the utility of sample size re-estimation can be questionable particularly when there are practical or funding difficulties associated with making any changes to planned sample sizes. Perhaps most importantly interim monitoring has the potential to identify selection bias, particularly in trials with post-randomisation identification or recruitment. Finally, the pragmatic nature of cluster trials might mean that the utility of methods to allow for interim monitoring of outcomes based on statistical testing, or monitoring for adherence to study interventions, are less relevant. Our intention is to facilitate the planning of future cluster randomised trials and to promote discussion and debate to improve monitoring of these studies.

Cost-effectiveness of mifepristone and misoprostol versus misoprostol alone for the management of missed miscarriage: an economic evaluation based on the MifeMiso trial.

OBJECTIVE: To assess the cost-effectiveness of mifepristone and misoprostol (MifeMiso) compared with misoprostol only for the medical management of a missed miscarriage. DESIGN: Within-trial economic evaluation and model-based analysis to set the findings in the context of the wider economic evidence for a range of comparators. Incremental costs and outcomes were calculated using nonparametric bootstrapping and reported using cost-effectiveness acceptability curves. Analyses were performed from the perspective of the UK's National Health Service (NHS). SETTING: Twenty-eight UK NHS early pregnancy units. SAMPLE: A cohort of 711 women aged 16-39 years with ultrasound evidence of a missed miscarriage. METHODS: Treatment with mifepristone and misoprostol or with matched placebo and misoprostol tablets. MAIN OUTCOME MEASURES: Cost per additional successfully managed miscarriage and quality-adjusted life years (QALYs). RESULTS: For the within-trial analysis, MifeMiso intervention resulted in an absolute effect difference of 6.6% (95% CI 0.7-12.5%) per successfully managed miscarriage and a QALYs difference of 0.04% (95% CI -0.01 to 0.1%). The average cost per successfully managed miscarriage was lower in the MifeMiso arm than in the placebo and misoprostol arm, with a cost saving of £182 (95% CI £26-£338). Hence, the MifeMiso intervention dominated the use of misoprostol alone. The model-based analysis showed that the MifeMiso intervention is preferable, compared with expectant management, and this is the current medical management strategy. However, the model-based evidence suggests that the intervention is a less effective but less costly strategy than surgical management. CONCLUSIONS: The within-trial analysis found that based on cost-effectiveness grounds, the MifeMiso intervention is likely to be recommended by decision makers for the medical management of women presenting with a missed miscarriage. TWEETABLE ABSTRACT: The combination of mifepristone and misoprostol is more effective and less costly than misoprostol alone for the management of missed miscarriages.

The FAST-M complex intervention for the detection and management of maternal sepsis in low-resource settings: a multi-site evaluation.

OBJECTIVE: To evaluate whether the implementation of the FAST-M complex intervention was feasible and improved the recognition and management of maternal sepsis in a low-resource setting. DESIGN: A before-and-after design. SETTING: Fifteen government healthcare facilities in Malawi. POPULATION: Women suspected of having maternal sepsis. METHODS: The FAST-M complex intervention consisted of the following components: the FAST-M maternal sepsis treatment bundle and the FAST-M implementation programme. Performance of selected process outcomes was compared between a 2-month baseline phase and 6-month intervention phase with compliance used as a proxy measure of feasibility. MAIN OUTCOME RESULT: Compliance with vital sign recording and use of the FAST-M maternal sepsis bundle. RESULTS: Following implementation of the FAST-M intervention, women were more likely to have a complete set of vital signs taken on admission to the wards (0/163 [0%] versus 169/252 [67.1%], P < 0.001). Recognition of suspected maternal sepsis improved with more cases identified following the intervention (12/106 [11.3%] versus 107/166 [64.5%], P < 0.001). Sepsis management improved, with women more likely to receive all components of the FAST-M treatment bundle within 1 hour of recognition (0/12 [0%] versus 21/107 [19.6%], P = 0.091). In particular, women were more likely to receive antibiotics (3/12 [25.0%] versus 72/107 [67.3%], P = 0.004) within 1 hour of recognition of suspected sepsis. CONCLUSION: Implementation of the FAST-M complex intervention was feasible and led to the improved recognition and management of suspected maternal sepsis in a low-resource setting such as Malawi. TWEETABLE ABSTRACT: Implementation of a sepsis care bundle for low-resources improved recognition & management of maternal sepsis.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Maternal characteristics and causes associated with refractory postpartum haemorrhage after vaginal birth: a secondary analysis of the WHO CHAMPION trial data.

OBJECTIVE: To assess the maternal characteristics and causes associated with refractory postpartum haemorrhage (PPH). DESIGN: Secondary analysis of the WHO CHAMPION trial data. SETTING: Twenty-three hospitals in ten countries. POPULATION: Women from the CHAMPION trial who received uterotonics as first-line treatment of PPH. METHODS: We assessed the association between sociodemographic, pregnancy and childbirth factors and refractory PPH, and compared the causes of PPH between women with refractory PPH and women responsive to first-line PPH treatment. MAIN OUTCOME MEASURES: Maternal characteristics; causes of PPH. RESULTS: Women with labour induced or augmented with uterotonics (adjusted odds ratio [aOR] 1.35; 95% CI 1.07-1.72), with episiotomy or tears requiring suturing (aOR 1.82; 95% CI 1.34-2.48) and who had babies with birthweights ≥3500 g (aOR 1.33; 95% CI 1.04-1.69) showed significantly higher odds of refractory PPH compared with the reference categories in the multivariate analysis adjusted by centre and trial arm. While atony was the sole PPH cause in 53.2% (116/218) of the women in the responsive PPH group, it accounted for only 31.5% (45/143) of the causes in the refractory PPH group. Conversely, tears were the sole cause in 12.8% (28/218) and 28% (40/143) of the responsive PPH and refractory PPH groups, respectively. Placental problems were the sole cause in 11 and 5.6% in the responsive and refractory PPH groups, respectively. CONCLUSION: Women with refractory PPH showed a different pattern of maternal characteristics and PPH causes compared with those with first-line treatment responsive PPH. TWEETABLE ABSTRACT: Women with refractory postpartum haemorrhage are different from those with first-line treatment responsive PPH.

Development of the FAST-M maternal sepsis bundle for use in low-resource settings: a modified Delphi process.

OBJECTIVE: To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings. DESIGN: Modified Delphi process. SETTING: Participants from 34 countries. POPULATION: Healthcare practitioners working in low resource settings (n = 143; 34 countries), members of an expert panel (n = 11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group. METHODS: We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in-person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering their use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts. MAIN OUTCOME MEASURE: Consensus on bundle items. RESULTS: Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: (1) Fluids, (2) Antibiotics, (3) Source identification and control, (4) Transfer (to appropriate higher-level care) and (5) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym 'FAST-M'. CONCLUSION: A clinically relevant maternal sepsis bundle for low resource settings has been developed by international consensus. TWEETABLE ABSTRACT: A maternal sepsis bundle for low resource settings has been developed by international consensus.

Caesarean scar pregnancy in the UK: a national cohort study.

OBJECTIVE: To estimate the incidence of caesarean scar pregnancy (CSP) and to describe the management outcomes associated with this condition. DESIGN: A national cohort study using the UK Early Pregnancy Surveillance Service (UKEPSS). SETTING: 86 participating Early Pregnancy Units. POPULATION: All women diagnosed in the participating units with CSP between November 2013 and January 2015. METHODS: Cohort study of women identified through the UKEPSS monthly mailing system. MAIN OUTCOME MEASURES: Incidence, clinical outcomes and complications. RESULTS: 102 cases of CSP were reported, with an estimated incidence of 1.5 per 10 000 (95% CI 1.1-1.9) maternities. Full outcome data were available for 92 women. Management was expectant in 21/92 (23%), medical in 15/92 (16%) and surgical in 56/92 (61%). The success rates of expectant, medical and surgical management were 43% (9/21), 46% (7/15) and 96% (54/56), respectively. The complication rates were 15/21 (71%) with expectant, 9/15 (60%) with medical and 20/56 (36%) with surgical management. Discharge from care (median number of days) was 82 (range 37-174) with expectant, 21 (range 10-31) with medical and 11 (range 4-49) with surgical management. CONCLUSIONS: Surgical management appears to be associated with a high success rate, low complication rate and short post-treatment follow up. TWEETABLE ABSTRACT: Surgery for CSP appears to be successful, with low complication rates and short post-treatment follow up.

Fallopian tube catheterization in the treatment of proximal tubal obstruction: a systematic review and meta-analysis.

Study question: What is the chance of clinical pregnancy when fallopian tube catheterization is used for proximal tubal obstruction? Summary answer: The pooled clinical pregnancy rate of tubal catheterization after proximal tubal obstruction is 27% (95% CI 25-30%). What is known already: Restoring fallopian tube patency by performing tubal catheterization has fallen out of favour since the increased availability of IVF. Our study is the first systematic review and meta-analysis to investigate reproductive outcomes following tubal catheterization for proximal tubal obstruction. Study design, size, duration: We undertook a systematic review and meta-analysis of 27 observational studies consisting of 1720 patients undergoing tubal catheterization for proximal tubal obstruction, who attempted to conceive naturally after the procedure. Participants/materials, setting, methods: Systematic literature searches were performed in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A total of 2195 titles and abstracts were reviewed. Only studies that reported outcomes when tubal catheterization was performed with no other tubal surgery were included. Twenty-seven cohort studies matched the inclusion criteria for the meta-analysis. Main results and the role of chance: The meta-analysis showed a pooled clinical pregnancy rate of 27% (95% CI 25-30%) after the use of tubal catheterization for unilateral or bilateral proximal tubal obstruction (27 studies, 1556 patients). In women with bilateral obstruction (14 studies, 617 patients), the clinical pregnancy rate was 27% (95% CI 23-32%). Our meta-analysis demonstrated that the pooled cumulative clinical pregnancy rates were 22.3% (95% CI 17.8-27.8%) at 6 months, 25.8% (95% CI 21.1-31.5%) at 9 months, 26.4% (95% CI 23.0-30.2%) at 12 months, 26.0% (95% CI 22.8-29.7%) at 18 months, 27.0% (95% CI 24.0-30.5%) at 24 months, 27.9% (95% CI 24.9-31.3%) at 36 months and 28.5% (95% CI 25.5-31.8%) at 48 months. The pooled live birth rate (14 studies, 551 patients) was 22% (95% CI 18-26%). The pooled ectopic pregnancy rate (27 studies, 1556 patients) was 4% (95% CI 3-5%). The included studies scored satisfactorily on the Newcastle-Ottawa quality assessment scale. Limitations, reasons for caution: The pooled clinical pregnancy rate after tubal catheterization was found to be almost comparable to that after IVF. However, included studies were small, non-comparative series with significant clinical heterogeneity in population characteristics, follow-up and surgical equipment, technique and experience. Wider implications of the findings: These findings suggest fallopian tube catheterization as an alternative strategy to IVF in patients presenting with proximal tubal obstruction. Further research should focus on comparing different surgical techniques of fallopian tube catheterization with IVF and provide cumulative reproductive outcomes over long-term follow-up. Study funding/competing interest(s): No funding was required and the authors have no competing interests to declare. Registration number: N/A.

Psychological morbidity associated with hyperemesis gravidarum: a systematic review and meta-analysis.

BACKGROUND: Psychological illness occurring in association with hyperemesis gravidarum (HG) has been widely reported. OBJECTIVE: To determine if there is a higher incidence of psychological morbidity in women with HG compared with women without significant nausea and vomiting in pregnancy. SEARCH STRATEGY: PubMed, MEDLINE, Embase and PsychINFO were searched up to September 2015. SELECTION CRITERIA: Articles referring to psychological morbidity in relation to HG. For meta-analysis case-control studies using numerical scales to compare psychological symptoms. DATA COLLECTION AND ANALYSIS: Articles were independently assessed for inclusion by two reviewers and methodology was appraised using the Newcastle Ottawa Scale. Comparison was made using the standard mean difference (SMD) in symptom scale scores. MAIN RESULTS: In all, 59 articles were included in the systematic review, 12 of these were used in the meta-analysis. Meta-analysis of depression scale scores demonstrated a very large effect with statistically significantly higher depression scale scores in women with HG (SMD 1.22; 95% CI 0.80-1.64; P ≤ 0.01) compared with controls. Meta-analysis of anxiety scores demonstrated a large effect with statistically significantly higher anxiety disorder scale scores in women with HG (SMD 0.86; 95% CI 0.53-1.19; P ≤ 0.01). In both analyses significant heterogeneity was identified (depression and HG I2  = 94%, P ≤ 0.01; anxiety and HG I2  = 84%, P = 0.02). CONCLUSIONS: Our systematic review and meta-analysis have shown a significantly increased frequency of depression and anxiety in women with HG. The findings should prompt service development for women with HG that includes provision of psychological care and support. TWEETABLE ABSTRACT: Meta-analysis demonstrates an increase in #PsychologicalMorbidity in women with #HyperemesisGravidarum.

The effectiveness of gynaecology teaching associates in teaching pelvic examination to medical students: a randomised controlled trial.

OBJECTIVES: To assess whether teaching female pelvic examinations using gynaecological teaching associates (GTAs); women who are trained to give instruction and feedback on gynaecological examination technique, improves the competence, confidence and communication skills of medical students compared to conventional teaching. STUDY DESIGN: Randomised controlled trial. SETTING: Ten University of Birmingham (UoB) affiliated teaching hospitals in the UK. POPULATION: 492 final year medical students. METHODS: GTA teaching of gynaecological examination compared with conventional pelvic manikin based teaching at the start of a five week clinical placement in obstetrics and gynaecology (O&G). MAIN OUTCOME MEASURES: Student's perception of their confidence was measured on a 10cm visual analogue scale (VAS). Domains of competence were measured by a senior clinical examiner using a standardised assessment tool which utilised 10cm VAS and by a GTA using a four point Likert scale. Assessors were blinded to the allocated teaching intervention. RESULTS: 407/492 (83%) students completed both the intervention and outcome assessment. Self-reported confidence was higher in students taught by GTAs compared with those taught on manikins (median score GTA 6.3; vs. conventional 5.8; p=0.03). Competence was also higher in those taught by GTAs when assessed by an examiner (median global score GTA 7.1 vs. conventional 6.0; p<0.001) and by a GTA (p<0.001). CONCLUSIONS: GTA teaching of female pelvic examination at the start of undergraduate medical student O&G clinical placements improves their confidence and competence compared with conventional pelvic manikin based teaching. GTAs should be introduced into undergraduate medical curricula to teach pelvic examination.

Accuracy of first-trimester ultrasound in diagnosis of tubal ectopic pregnancy in the absence of an obvious extrauterine embryo: systematic review and meta-analysis.

OBJECTIVES: To determine the accuracy of ultrasound in the diagnosis of a tubal ectopic pregnancy in the absence of an obvious extrauterine embryo. METHODS: This was a systematic review conducted in accordance with the PRISMA statement and registered with PROSPERO. We searched MEDLINE, EMBASE and The Cochrane Library for relevant citations from database inception to July 2014. Studies were selected in a two-stage process and their data extracted by two reviewers. Accuracy measures were calculated for each ultrasound sign, i.e. empty uterus, pseudosac, adnexal mass and free fluid in the pouch of Douglas, alone and in various combinations. Individual study estimates were plotted in summary receiver-operating characteristics curves and forest plots for examination of heterogeneity. The quality of included studies was assessed. RESULTS: Thirty-one studies including 5858 women were selected from 19,959 citations. Following meta-analysis, an empty uterus on ultrasound was found to predict an ectopic pregnancy with a sensitivity of 81.1% (95% CI, 42.1-96.2%) and specificity of 79.5% (95% CI, 68.9-87.1%). The corresponding performance of the pseudosac, adnexal mass and free fluid were: 5.5% (95% CI, 3.3-9.0%) and 94.2% (95% CI, 75.9-98.8%); 63.5% (95% CI, 48.5-76.3%) and 91.4% (95% CI, 83.6-95.7%); and 47.2% (95% CI, 33.2-61.7%) and 92.3% (95% CI, 85.6-96.0%), respectively. CONCLUSION: Visualization of an empty uterus, adnexal mass, free fluid or a pseudosac has poor sensitivity for the diagnosis of a tubal pregnancy when an obvious extrauterine embryo is absent, but it has good specificity. We can therefore infer that ultrasound is more useful for 'ruling in' a tubal pregnancy than 'ruling out' one. However, the findings were limited by the poor quality of some included studies and heterogeneity in the index test and reference standard.

Salpingostomy in the treatment of hydrosalpinx: a systematic review and meta-analysis.

STUDY QUESTION: What is the chance of natural conception when salpingostomy is used to treat hydrosalpinx?. SUMMARY ANSWER: The natural clinical pregnancy rate following salpingostomy is 27%, in the hands of experienced surgeons who publish their results. WHAT IS KNOWN ALREADY: Tubal surgery is not commonly offered for women with hydrosalpinges since the advent of assisted conception treatment. This is the first systematic review to investigate natural conception rates following salpingostomy in the treatment of hydrosalpinx. STUDY DESIGN, SIZE, DURATION: A systematic review and meta-analysis of 22 observational studies encompasses 2810 patients undergoing salpingostomy and attempting natural conception. PARTICIPANTS/MATERIALS, SETTING, METHODS: Literature searches were conducted to retrieve observational studies which reported salpingostomy for hydrosalpinx. Databases searched included MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL, with no language restriction. Only studies that focused on salpingostomy (rather than other tubal conserving surgeries) for the treatment of hydrosalpinx were included. A total of 22 studies matched the inclusion criteria. MAIN RESULTS AND THE ROLE OF CHANCE: The pooled natural clinical pregnancy rate from the 22 observational studies (including 2810 patients) was 27% (95% confidence interval (CI): 25-29%) after salpingostomy was performed for hydrosalpinx. The cumulative clinical pregnancy rates were 8.7% (95% CI: 6.6-11.5%) at 6 months, 13.3% (95% CI: 10.6-16.7%) at 9 months, 20.0% (95% CI: 17.5-22.8%) at 12 months, 21.2% (95% CI: 18.6-24.1%) at 18 months and 25.5% (95% CI: 22.2-29.4%) at 24 months after salpingostomy. The pooled live birth rate (10 studies, 1469 patients) was 25% (95% CI: 22-28%) after salpingostomy was performed for hydrosalpinx. The pooled ectopic pregnancy rate (19 studies, 2662 patients) was 10% (95% CI: 9-11%). The pooled miscarriage rate (seven studies, 924 patients) was 7% (95% CI: 6-9%). The included studies scored well on the Newcastle Ottawa quality assessment scale. LIMITATIONS, REASONS FOR CAUTION: Strict inclusion criteria were used in the conduct of the systematic review. However, the studies included are clinically heterogeneous in many aspects including patient characteristics, surgical technique and duration of follow-up after salpingostomy. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this systematic review suggest that salpingostomy is an alternative treatment strategy to tubal clipping or salpingectomy in patients presenting to fertility services with hydrosalpinx. Further prospective, large and high quality studies are needed to identify the subpopulation that would most benefit from tube conserving surgery. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Accuracy of first-trimester ultrasound in diagnosis of intrauterine pregnancy prior to visualization of the yolk sac: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the diagnostic accuracy of ultrasound in predicting the location of an intrauterine pregnancy before visualization of the yolk sac is possible. METHODS: This was a systematic review conducted in accordance with the PRISMA statement and registered with PROSPERO. We searched MEDLINE, EMBASE and The Cochrane Library for relevant citations. Studies were selected in a two-stage process and their data extracted by two reviewers. Accuracy measures were calculated for each ultrasound sign, i.e. gestational sac, double decidual sac sign, intradecidual sign, chorionic rim sign and yolk sac. Individual study estimates were plotted in summary receiver-operating characteristics curves and forest plots for examination of heterogeneity. The quality of included studies was assessed. RESULTS: Seventeen studies including 2564 women were selected from 19 959 potential papers. Following meta-analysis, the presence of a gestational sac on ultrasound examination was found to predict an intrauterine pregnancy with a sensitivity of 52.8% (95% CI, 38.2-66.9%) and specificity of 97.6% (95% CI, 94.3-99.0%). The corresponding performance of the double decidual sac sign, intradecidual sign, chorionic rim sign and yolk sac were: 81.8% (95% CI, 68.1-90.4%) and 97.3% (95% CI, 76.1-99.8%); 66.1% (95% CI, 58.9-72.8%) and 100% (95% CI, 91.0-100%); 79.9% (95% CI, 73.0-85.7%) and 97.1% (95% CI, 89.9-99.6%); and 42.2% (95% CI, 27.7-57.9%) and 100% (95% CI, 54.1-100%), respectively. CONCLUSION: Visualization of a gestational sac, double decidual sac sign, intradecidual sign or chorionic rim sign increases the probability of an intrauterine pregnancy but is not as accurate for diagnosis as the detection of the yolk sac. However, the findings were limited by the small number and poor quality of the studies included and heterogeneity in the index test and reference standard.

The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis.

BACKGROUND: Endometriosis is found in 0.5-5% of fertile women and 25-40% of infertile women. It is known that endometriosis is associated with infertility, but there is uncertainty whether women with endometriosis have adverse pregnancy outcomes in in vitro fertilisation (IVF) treatment. OBJECTIVES: To explore the association between endometriosis and IVF outcome. SEARCH STRATEGY: Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science (inception, December 2012) in all languages, together with reference lists of retrieved papers. SELECTION CRITERIA: Studies comparing IVF outcome in women with endometriosis with women without endometriosis. Patients were classified by stage of endometriosis. The outcomes were fertilisation, implantation, clinical pregnancy and live birth rates. Study selection was conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. DATA COLLECTION AND ANALYSIS: Data extraction was conducted independently by two reviewers. Relative risks from individual studies were meta-analysed. MAIN RESULTS: Twenty-seven observational studies were included, comprising 8984 women. Meta-analysis of these studies showed that fertilisation rates were reduced in stage I/II of endometriosis (relative risk [RR] = 0.93, 95% confidence interval [95% CI] 0.87-0.99, P = 0.03). There was a decrease in the implantation rate (RR = 0.79, 95% CI 0.67-0.93, P = 0.006) and clinical pregnancy rate (RR = 0.79, 95% CI 0.69-0.91, P = 0.0008) in women with stage III/IV endometriosis undergoing IVF treatment. CONCLUSION: The presence of severe endometriosis (stage III/IV) is associated with poor implantation and clinical pregnancy rates in women undergoing IVF treatment.

Pre-eclampsia is associated with, and preceded by, hypertriglyceridaemia: a meta-analysis.

BACKGROUND: Elevated triglycerides are a feature of the metabolic syndrome, maternal obesity, maternal vasculitis (i.e. systemic lupus erythematosus) and diabetes mellitus. These conditions are all known risk factors for pre-eclampsia. Hypertriglyceridaemia therefore may be associated with pre-eclampsia and indeed this may precede the presence of overt disease. OBJECTIVE: In this study we determine the association between hypertriglyceridaemia and pre-eclampsia in pregnant women. SEARCH STRATEGY: We searched MEDLINE, EMBASE, Web of Science, Excerpta Medica Database, ISI Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library from inception until June 2012 and reference lists of relevant studies. SELECTION CRITERIA: Two reviewers independently selected studies on pregnant women where triglycerides were measured and women were followed up until the development of pre-eclampsia or selected on the basis of presence of pre-eclampsia and compared with controls. DATA COLLECTION AND ANALYSIS: We collected and meta-analysed the weighted mean differences (WMDs) of triglyceride levels from individual studies using a random effects model. MAIN RESULTS: We found strong evidence from meta-analysis of 24 case-control studies (2720 women) that pre-eclampsia is associated with higher levels of serum triglycerides (WMD 0.78 mmol/l, 95% confidence interval 0.6-0.96, P < 0.00001). This finding is also confirmed in five cohort studies, that recruited 3147 women in the second trimester before the onset of pre-eclampsia, which proves that hypertriglyceridaemia precedes the onset of pre-eclampsia (WMD 0.24 mmol/l, 95% confidence interval 0.13-0.34, P < 0.0001). AUTHOR'S CONCLUSIONS: Hypertriglyceridaemia is associated with and precedes the onset of pre-eclampsia. Further research should focus on defining the prognostic accuracy of this test to identify women at risk and the beneficial effect of triglyceride-lowering therapies in pregnancy.

Dexamethasone reduces pain, vomiting and overall complications following tonsillectomy in adults: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Tonsillectomy is one of the most common surgical procedures, but there is debate whether systemic steroids should be used to reduce pain and post-operative complications. OBJECTIVE OF REVIEW: To determine whether peri-operative steroids reduce post-tonsillectomy pain and complications in adults. TYPE OF REVIEW: Systematic review and meta-analysis of randomised controlled trials. SEARCH STRATEGY: We searched MEDLINE (1950-2010), EMBASE (1980-2010), CINAHL (1981-2010), Web of Science, ProQuest, metaRegister, Conference Proceedings Citation Index, the Cochrane Library and reference lists of relevant studies. EVALUATION METHOD: Two reviewers independently selected trials and extracted data on their quality, characteristics and results. Trials included adults (age >16 years) undergoing elective tonsillectomy where peri-operative steroids were used, and the results were compared with control or placebo. RESULTS: There were seven randomised controlled trials (580 patients) reporting post-operative pain. Meta-analysis demonstrates that dexamethasone in adults reduces the pain level experienced in the first post-tonsillectomy day [standard mean difference (SMD): -0.63, 95% CI: -1.13 to -0.12] with significant heterogeneity (I(2) = 84%, P < 0.00001). Sub-group analysis to explore heterogeneity demonstrated this reduction in pain was mostly with high total dose steroids (total >10 mg over first 24 h post-operatively; SMD: -1.48, 95% CI: -2.17 to -0.79, P < 0.00001), especially when given both intra-operatively and post-operatively. There was no significant effect with low doses (SMD: -0.12, 95% CI: -0.36 to 0.13, P = 0.35). There were three trials (231 patients) that reported post-operative nausea and vomiting, three other trials (270 patients) reporting on bleeding and three trials (401 patients) reporting other complications (infections and odynophagia). There was a significant reduction in post-operative nausea and vomiting (RR: 0.53, 95% CI: 0.36 to 0.80, P = 0.002, I(2) = 26%) and bleeding (RR: 0.45, 95% CI: 0.25 to 0.80, P = 0.007, I(2) = 0%), but the reduction in the other complications did not reach statistical significance (RR: 0.69, 95% CI: 0.48 to 1.01, P = 0.06, I(2) = 0%). Pooling of these complications (post-operative nausea and vomiting, bleeding, infections and odynophagia) shows that in six trials (501 patients), the use of dexamethasone significantly reduced post-operative complications following tonsillectomy in adults (RR: 0.59, 95% CI: 0.49 to 0.71, P < 0.00001, I(2) = 0%), when compared with placebo or control. CONCLUSIONS: Dexamethasone reduces pain, post-operative nausea and vomiting, bleeding and overall post-operative complications in adults undergoing tonsillectomy. However, the effect of the dose of dexamethasone on post-operative pain and whether dexamethasone reduces bleeding require further research.