The effectiveness of kangaroo mother care in lowering postpartum depression in mothers of preterm and low birth weight babies: a systematic review and meta-analysis.

Background: Kangaroo mother care (KMC) intervention involves skin-to-skin contact between mother and infant. Some studies have shown a decrease in postpartum depression (PPD) in mothers of preterm and low birth weight (LBW) infants. However, the literature is scattered and of variable quality. Aims: To conduct a systematic review of available literature and provide a comprehensive picture of the effect of KMC on PPD among mothers of preterm and LBW infants. Methods: The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. After PROSPERO registration, a systematic search was conducted using PubMed, Cochrane Central Library, and Google Scholar from the inception of the databases till 14 June 2021. Of the 2944 studies assessed for titles and abstracts, nine studies with 2042 participants were included in the review. Included articles targeted mothers with LBW (<2500 g) or preterm infants (<37 weeks), used an authentic PPD tool, and had standard care or an incubator as the control group. Studies not published in English and in which mothers had a previous psychiatric illness were excluded. The risk of bias was assessed using the Cochrane Risk of Bias Tool for randomized control trials and the Newcastle-Ottawa Scale for observational studies. All the results were converted to standard mean deviation and pooled together using a random-effects model with a 95% CI. A P-value of less than 0.05 is considered significant. Results: KMC Intervention was significantly associated with a lower depression score than control groups. The reduction in depression in the intervention (KMC) group was moderate: SMD=-0.38 (-0.68 to -0.08; 95% CI; I 2=86%; P=0.013). No significant difference was found between the PPD scores of both groups using the Edinburgh Postpartum Depression Scale score. Conclusions: The authors conclude that the negative effects of LBW and preterm birth experience on maternal mental health can be avoided to a moderate degree by KMC. Due to a lack of methodological uniformity, different scales for outcome measurement, and discrepancies in intervention features, significantly high heterogeneity was detected. The authors need further larger-scale studies with a uniform study design to better predict the efficacy of KMC better.

Smell Dysfunction in Patients with Primary Sjögren's Syndrome: Impact on Quality of Life.

OBJECTIVES: Patients with primary Sjögren's syndrome (pSS) often report smell and taste disturbances. However, the correlation between smell impairment and mucosal dryness is not well understood. The objectives of this study were to investigate the following: (1) the prevalence of smell hypofunction in patients with SS; (2) the impact of smell hypofunction on their quality of life (QoL); (3) whether the patients' smell is correlated with xerostomia; and (4) whether the patients' smell is affected by taste hypofunction, disease duration, age, smoking or self-reported neuropathy. METHODOLOGY: An ethically approved cross-sectional study was conducted on 65 female patients with SS and 62 sex-matched healthy controls. Their smell was assessed using the University of Pennsylvania Smell Identification Test. Their taste acuity was assessed using the Taste Strips Test. A visual analogue scale was used for the self-assessment of smell and taste functions. Xerostomia was assessed by the salivary flow rate, clinical oral dryness score and the Xerostomia Inventory. The patients' QoL and mental health well-being were assessed using validated questionnaires. RESULTS: In the SS group, the patients' smell function was impaired in 27/65 patients compared with the controls (15/62, p < 0.05), and it did not correlate with the severity of xerostomia, taste acuity (r = 0.05, p = 0.6) or self-reported nasal dryness (r = -0.02, p = 0.7). In the patients' group, smell hypofunction was not correlated with disease duration (ß = 0.1, 95% CI = -0.07-0.1) or smoking (ß = -0.02, 95% CI = -8-7). Age was not correlated with the smell function in the patients' group (ß = -0.1, p = 0.5) but was correlated significantly with smell in the healthy participants' group (ß = -0.3, p = 0.02). Neuropathy affected 81.2% of the patients' group. Their QoL and mental health well-being were not affected by smell hypofunction. CONCLUSION: Smell hypofunction appears to be a clinical manifestation in patients with SS, but it does not seem to be associated with the severity of mucosal dryness or with taste disturbance.

Gender bias in shared decision-making among cancer care guidelines: A systematic review.

BACKGROUND: In cancer care, the promotion and implementation of shared decision-making in clinical practice guidelines (CPG) and consensus statements may have potential differences by gender. OBJECTIVE: To systematically analyse recommendations concerning shared decision-making in CPGs and consensus statements for the most frequent cancers exclusively among males (prostate) and females (endometrial). SEARCH STRATEGY: We prospectively registered the protocol at PROSPERO (ID: RD42021241127). MEDLINE, EMBASE, Web of Science, Scopus and online sources (8 guideline databases and 65 professional society websites) were searched independently by two reviewers, without language restrictions. INCLUSION CRITERIA: CPGs and consensus statements about the diagnosis or treatment of prostate and endometrial cancers were included from January 2015 to August 2021. DATA EXTRACTION AND SYNTHESIS: Quality assessment deployed a previously developed 31-item tool and differences between the two cancers analysed. MAIN RESULTS: A total of 176 documents met inclusion criteria, 97 for prostate cancer (84 CPGs and 13 consensus statements) and 79 for endometrial cancer (67 CPGs and 12 consensus statements). Shared decision-making was recommended more often in prostate cancer guidelines compared to endometrial cancer (46/97 vs. 13/79, 47.4% vs. 16.5%; p < .001). Compared to prostate cancer guidelines (mean 2.14 items, standard deviation 3.45), compliance with the shared-decision-making 31-item tool was lower for endometrial cancer guidelines (mean 0.48 items, standard deviation 1.29) (p < .001). Regarding advice on the implementation of shared decision-making, it was only reported in 3 (3.8%) endometrial cancer guidelines and in 16 (16.5%) prostate cancer guidelines (p < .001). DISCUSSION AND CONCLUSIONS: We observed a significant gender bias as shared decision-making was systematically more often recommended in the prostate compared to endometrial cancer guidelines. These findings should encourage new CPGs and consensus statements to consider shared decision-making for improving cancer care regardless of the gender affected. PATIENT OR PUBLIC CONTRIBUTION: The findings may inform future recommendations for professional associations and governments to update and develop high-quality clinical guidelines to consider patients' preferences and shared decision-making in cancer care.

Predicting major complications in patients undergoing laparoscopic and open hysterectomy for benign indications.

BACKGROUND: Hysterectomy, the most common gynecological operation, requires surgeons to counsel women about their operative risks. We aimed to develop and validate multivariable logistic regression models to predict major complications of laparoscopic or abdominal hysterectomy for benign conditions. METHODS: We obtained routinely collected health administrative data from the English National Health Service (NHS) from 2011 to 2018. We defined major complications based on core outcomes for postoperative complications including ureteric, gastrointestinal and vascular injury, and wound complications. We specified 11 predictors a priori. We used internal-external cross-validation to evaluate discrimination and calibration across 7 NHS regions in the development cohort. We validated the final models using data from an additional NHS region. RESULTS: We found that major complications occurred in 4.4% (3037/68 599) of laparoscopic and 4.9% (6201/125 971) of abdominal hysterectomies. Our models showed consistent discrimination in the development cohort (laparoscopic, C-statistic 0.61, 95% confidence interval [CI] 0.60 to 0.62; abdominal, C-statistic 0.67, 95% CI 0.64 to 0.70) and similar or better discrimination in the validation cohort (laparoscopic, C-statistic 0.67, 95% CI 0.65 to 0.69; abdominal, C-statistic 0.67, 95% CI 0.65 to 0.69). Adhesions were most predictive of complications in both models (laparoscopic, odds ratio [OR] 1.92, 95% CI 1.73 to 2.13; abdominal, OR 2.46, 95% CI 2.27 to 2.66). Other factors predictive of complications included adenomyosis in the laparoscopic model, and Asian ethnicity and diabetes in the abdominal model. Protective factors included age and diagnoses of menstrual disorders or benign adnexal mass in both models and diagnosis of fibroids in the abdominal model. INTERPRETATION: Personalized risk estimates from these models, which showed moderate discrimination, can inform clinical decision-making for people with benign conditions who may require hysterectomy.

Is minimally invasive orthopedic surgery safer than open? A systematic review of systematic reviews.

BACKGROUND: To assess the safety of minimally invasive surgery (MIS) for orthopedic spinal, upper limb and lower limb procedures, this systematic review of systematic reviews compared their complications with open procedures. MATERIALS AND METHODS: A literature search was conducted electronically (PubMed, Cochrane library and Web of Science; May 8, 2021) without language restriction in the past five years. Reviews that consulted at least two databases, compared MIS with open orthopedic surgery, and reported the following: intraoperative, post-operative or total complications, function, ambulation, pain, hospital stay, reoperation rate and operation time were included. Article selection, quality assessment using AMSTAR-2, and data extraction were conducted in duplicate on predesigned forms. In each review, a subset analysis focusing on prospective cohort and randomized studies was additionally performed. PROSPERO: CRD42020178171. RESULTS: The search yielded 531 articles from which 76 reviews consisting of 1104 primary studies were included. All reviews were assessed as being low quality. Compared to open surgery, MIS had fewer total, postoperative and intraoperative complications in 2/10, 2/11 and 2/5 reviews of spinal procedures respectively, 1/3, 1/4 and 1/2 reviews of upper limb procedures respectively, and 4/6, 2/7 and 0/2 reviews of lower limb procedures respectively. CONCLUSIONS: MIS had greater overall safety compared to open surgery in spinal procedures. In upper limb and lower limb procedures, MIS was not outright superior to open procedures in terms of safety hence a general preference of MIS is not justified on the premise of a better safety profile compared to open procedures.

Personalising the risk of conversion from laparoscopic to open hysterectomy in benign conditions: Development and external validation of risk prediction models.

OBJECTIVE: To develop and validate novel prediction models to personalise the risk of conversion from laparoscopic to open hysterectomy in benign conditions. DESIGN: Retrospective cohort study. SETTINGS: English NHS Hospitals between 2011 and 2018. POPULATION: 68 752 women undergoing laparoscopic hysterectomy for benign conditions. METHODS: We developed two multivariable logistic models using readily available clinical information, one for the pre-operative setting and another for operative decision-making using additional surgical information, using 2011-2016 data in five regions (24 806 women). We validated them (a) temporally in the same regions using 2017-2018 data (12 438 women); (b) geographically in the same time-period using data from three different regions (22 024 women); and (c) temporally and geographically using 2017-2018 data in three different regions (9484 women). MAIN OUTCOME MEASURES: Conversion from laparoscopic to open hysterectomy. RESULTS: Conversions occurred in 6.8% (1687/24 806) of hysterectomies in the development group, and in 5.5% (681/12 438) in the temporal, 5.9% (1297/22 204) in the geographical and 5.2% (488/9484) in the temporal and geographical validation groups. In the development cohort, the area under the receiver operating characteristic curve values for the pre-operative and operative models were 0.65 and 0.67, respectively. In the validation cohorts the corresponding values were 0.65 and 0.66 (temporal), 0.66 and 0.68 (geographical) and 0.65 and 0.68 (temporal and geographical), respectively. Factors predictive of conversion included age, Asian ethnicity, obesity, fibroids, adenomyosis, endometriosis and adhesions. Adhesions were the most predictive (odds ratio 2.54, 95% confidence interval 2.22-2.90). CONCLUSION: The models for predicting conversions showed acceptable performance and transferability. TWEETABLE ABSTRACT: Novel tool to personalise the risk of conversion from laparoscopic to open hysterectomy in benign conditions.

Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis.

BACKGROUND: Numerous iron preparations are available for the treatment of iron deficiency anaemia in pregnancy. We aimed to provide a summary of the effectiveness and safety of iron preparations used in this setting. METHODS: We did a systematic review and network meta-analysis of randomised trials. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature for trials published in any language from Jan 1, 2011, to Feb 28, 2021. We included trials including pregnant women with iron deficiency anaemia and evaluating iron preparations, irrespective of administration route, with at least 60 mg of elemental iron, in comparison with another iron or non-iron preparation. Three authors independently selected studies, extracted data, and did a risk of bias assessment using the Cochrane tool (version 1.0). The primary outcome was the effectiveness of iron preparations, evaluated by changes in haemoglobin concentration at 4 weeks from baseline. The secondary outcomes were change in serum ferritin concentration at 4 weeks from baseline and treatment-related severe and non-severe adverse events. We did random-effects pairwise and network meta-analyses. Side-effects were reported descriptively for each trial. This study is registered with PROSPERO, CRD42018100822. FINDINGS: Among 3037 records screened, 128 full-text articles were further assessed for eligibility. Of the 53 eligible trials (reporting on 9145 women), 30 (15 interventions; 3243 women) contributed data to the network meta-analysis for haemoglobin and 15 (nine interventions; 1396 women) for serum ferritin. The risk of bias varied across the trials contributing to network meta-analysis, with 22 of 30 trials in the network meta-analysis for haemoglobin judged to have a high or medium global risk of bias. Compared with oral ferrous sulfate, intravenous iron sucrose improved both haemoglobin (mean difference 7·17 g/L, 95% CI 2·62-11·73; seven trials) and serum ferritin (mean difference 49·66 µg/L, 13·63-85·69; four trials), and intravenous ferric carboxymaltose improved haemoglobin (mean difference 8·52 g/L, 0·51-16·53; one trial). The evidence for other interventions compared with ferrous sulfate was insufficient. The most common side-effects with oral iron preparations were gastrointestinal effects (nausea, vomiting, and altered bowel movements). Side-effects were less common with parenteral iron preparations, although these included local pain, skin irratation, and, on rare occasions, allergic reactions. INTERPRETATION: Iron preparations for treatment of iron deficiency anaemia in pregnancy vary in effectiveness, with good evidence of benefit for intravenous iron sucrose and some evidence for intravenous ferric carboxymaltose. Clinicians and policy makers should consider the effectiveness of individual preparations before administration, to ensure effective treatment. FUNDING: None.

Determinants of successful guideline implementation: a national cross-sectional survey.

BACKGROUND: CPGs are not uniformly successful in improving care and several instances of implementation failure have been reported. Performing a comprehensive assessment of the barriers and enablers is key to developing an informed implementation strategy. Our objective was to investigate determinants of guideline implementation and explore associations of self-reported adherence to guidelines with characteristics of participants in China. METHODS: This is a cross-sectional survey, using multi-stage stratified typical sampling based on China's economic regional divisions (the East, the Middle, the West and the Northeast). 2-5 provinces were selected from each region. 2-3 cities were selected in each province, and secondary and tertiary hospitals from each city were included. We developed a questionnaire underpinned by recommended methods for the design and conduct of self-administered surveys and based on conceptual framework of guideline use, in-depth related literature analysis, guideline development manuals, related behavior change theory. Finally, multivariate analyses were performed using logistic regression to produce adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The questionnaire consisted of four sections: knowledge of methodology for developing guidelines; barriers to accessing guideline; barriers to guideline implementation; and methods for improving guideline implementation. There were 1732 participants (87.3% response rate) from 51 hospitals. Of these, 77.2% reported to have used guidelines frequently or very frequently. The key barriers to guideline use were lack of education or training (46.2%), and overly simplistic wording or overly broad scope of recommendations (43.8%). Level of adherence to guidelines was associated with geographical regions (the northeast P < 0.001; the west P = 0.02; the middle P < 0.001 compared with the east), hospital grades (P = 0.028), length of practitioners' practice (P = 0.006), education background (Ph.D., P = 0.027; Master, P = 0.002), evidence-based medicine skills acquired in work unit (P = 0.012), and medical specialty of practitioner (General Practice, P = 0.006; Surgery, P = 0.043). CONCLUSION: Despite general acknowledgement of the importance of guidelines, the use of guidelines was not as frequent as might have been expected. To optimize the likelihood of adherence to guidelines, guideline implementation should follow an actively developed dissemination plan incorporating features associated with adherence in our study.

Human Papillomavirus Same Genotype Persistence and Risk: A Systematic Review.

OBJECTIVE: The aim of the study was to examine whether high-grade cervical intraepithelial neoplasia (CIN) was more closely associated with human papillomavirus (HPV) same-genotype persistence (SGTP) versus clearance of prior infection with a subsequent infection by a new genotype (genotype switch [GS]), clearance of HPV infection, or acquisition of a new HPV infection after a negative infection status, during a follow-up testing subsequent to abnormal screening results. MATERIALS AND METHODS: MEDLINE, Cochrane Library, Health Technology Assessment, and clinicaltrials.gov were searched from January 2000 to July 2019 for prospective controlled trials and observational studies of women and retrospective studies using HPV assays with extended- or full-genotype reporting. The primary outcome was high-grade CIN after at least 2 rounds of testing. Overall quality of evidence for the risk estimate outcomes was assessed. Of the 830 identified abstracts, 66 full-text articles were reviewed, and 7 studies were included in the synthesis. The study protocol was registered with the PROSPERO International Prospective Register of Systematic Reviews (CRD42018091093). RESULTS: Continued HPV-positive women falls in 2 equally large groups: SGTP and GS. Sensitivity, positive predictive value, and positive likelihood ratio of SGTP were significantly higher than for GS. Human papillomavirus genotypes may be ranked into 3 tiers (immediate colposcopy, follow-up testing, return to routine screening), according to associated risk of persistence for high-grade CIN and to prevailing clinical action thresholds. CONCLUSIONS: There is moderately high-quality evidence to support the clinical utility of SGTP to improve risk discrimination for high-grade CIN compared with qualitative HPV testing without genotype-specific information.

Validation and development of models using clinical, biochemical and ultrasound markers for predicting pre-eclampsia: an individual participant data meta-analysis.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. OBJECTIVES: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. DESIGN: This was an individual participant data meta-analysis of cohort studies. SETTING: Source data from secondary and tertiary care. PREDICTORS: We identified predictors from systematic reviews, and prioritised for importance in an international survey. PRIMARY OUTCOMES: Early-onset (delivery at < 34 weeks' gestation), late-onset (delivery at ≥ 34 weeks' gestation) and any-onset pre-eclampsia. ANALYSIS: We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C-statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I2 and τ2. A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of individual predictors for pre-eclampsia as odds ratios with 95% confidence and prediction intervals. RESULTS: The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-eclampsia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C-statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-eclampsia, and lowest for the first-trimester clinical characteristics models to predict any pre-eclampsia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-eclampsia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-eclampsia. LIMITATIONS: Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the individual participant data. CONCLUSION: For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. FUTURE WORK: Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015029349. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 72. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Pre-eclampsia, a condition in pregnancy that results in raised blood pressure and protein in the urine, is a major cause of complications for the mother and baby. WHAT IS NEEDED?: A way of accurately identifying women at high risk of pre-eclampsia to allow clinicians to start preventative interventions such as administering aspirin or frequently monitoring women during pregnancy. WHERE ARE THE RESEARCH GAPS?: Although over 100 tools (models) have been reported worldwide to predict pre-eclampsia, to date their performance in women managed in the UK NHS is unknown. WHAT DID WE PLAN TO DO?: We planned to comprehensively identify all published models that predict the risk of pre-eclampsia occurring at any time during pregnancy and to assess if this prediction is accurate in the UK population. If the existing models did not perform satisfactorily, we aimed to develop new prediction models. WHAT DID WE FIND?: We formed the International Prediction of Pregnancy Complications network, which provided data from a large number of studies (78 studies, 25 countries, 125 researchers, 3,570,993 singleton pregnancies). We were able to assess the performance of 24 out of the 131 models published to predict pre-eclampsia in 11 UK data sets. The models did not accurately predict the risk of pre-eclampsia across all UK data sets, and their performance varied within individual data sets. We developed new prediction models that showed promising performance on average across all data sets, but their ability to correctly identify women who develop pre-eclampsia varied between populations. The models were more clinically useful when used in the care of first-time mothers pregnant with one child, compared to a strategy of treating them all as if they were at high-risk of pre-eclampsia. WHAT DOES THIS MEAN?: Before using the International Prediction of Pregnancy Complications models in various populations, they need to be adjusted for characteristics of the particular population and the setting of application.

Harmonising research outcomes for polycystic ovary syndrome: an international multi-stakeholder core outcome set.

STUDY QUESTION: What are the key core outcomes to be reported in studies on polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: We identified 3 generic and 30 specific core outcomes in 6 specialist domains: metabolic (8), reproductive (7), pregnancy (10), oncological (1), psychological (1) and long-term outcomes (1). WHAT IS KNOWN ALREADY: Research reporting PCOS is heterogeneous with high variation in outcome selection, definition and quality. STUDY DESIGN, SIZE, DURATION: Evidence synthesis and a modified Delphi method with e-surveys were used as well as a consultation meeting. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 71 health professionals and 123 lay consumers (women with lived experience of PCOS and members of advocacy and peer support groups) from 17 high-, middle- and low-income countries were involved in this analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The final core outcome set included 3 generic outcomes (BMI, quality of life, treatment satisfaction) that are applicable to all studies on women with PCOS and 30 specific outcomes that were categorised into six specialist domains: 8 metabolic outcomes (waist circumference, type 2 diabetes, insulin resistance, impaired glucose tolerance, hypertension, coronary heart disease, lipid profile, venous thromboembolic disease); 7 reproductive outcomes [viable pregnancy (confirmed by ultrasound including singleton, twins and higher multiples), clinical and biochemical hyperandrogenism, menstrual regularity, reproductive hormonal profile, chronic anovulation, ovulation stimulation success including the number of stimulated follicles ≥ 12 mm, incidence and severity of ovarian hyperstimulation syndrome]; 10 pregnancy outcomes (live birth, miscarriage, stillbirth, neonatal mortality, gestational weight gain, gestational diabetes, preterm birth, hypertensive disease in pregnancy, baby birth weight, major congenital abnormalities); 3 psychological outcomes (depression, anxiety, eating disorders); 1 oncological (abnormal endometrial proliferation including atypical endometrial hyperplasia and endometrial cancer); and 1 outcome in the long-term domain (long-term offspring metabolic and developmental outcomes). LIMITATIONS, REASONS FOR CAUTION: We involved lay consumers in all stages of study through e-surveys but not through focus groups, thereby limiting our understanding of their choices. We did not address the variations in the definitions and measurement tools for some of the core outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Implementing this core outcome set in future studies on women with PCOS will improve the quality of reporting and aid evidence synthesis. STUDY FUNDING/COMPETING INTEREST(S): Evidence synthesis was funded through the Australian government, National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS, and H.T. is funded through an NHMRC fellowship. B.H.A. is funded through an NIHR lectureship. All authors have no competing interest to declare.

Management of first-trimester miscarriage: a systematic review and network meta-analysis.

BACKGROUND: First-trimester miscarriage affects up to a quarter of women worldwide. With many competing treatment options available, there is a need for a comprehensive evidence synthesis. OBJECTIVES AND RATIONALE: We conducted a systematic review and network meta-analysis to assess the effectiveness and safety of treatment options for first-trimester miscarriage: expectant management (EXP), sharp dilation and curettage (D+C), electric vacuum aspiration (EVAC), manual vacuum aspiration (MVA), misoprostol alone (MISO), mifepristone+misoprostol (MIFE+MISO) and misoprostol plus electric vacuum aspiration (MISO+EVAC). SEARCH METHODS: We searched MEDLINE, Embase, CINAHL, AMED and Cochrane Library from inception till June 2018. We included randomized trials of women with first-trimester miscarriage (<14 weeks gestation) and conducted a network meta-analysis generating both direct and mixed evidence on the effectiveness and side effects of available treatment options. The primary outcome was complete evacuation of products of conception. We assessed the risk of bias and the global network inconsistency. We compared the surface under the cumulative ranking curve (SUCRA) for each treatment. OUTCOMES: A total of 46 trials (9250 women) were included. The quality of included studies was overall moderate with some studies demonstrating a high risk of bias. We detected unexplained inconsistency in evidence loops involving MIFE+MISO and adjusted for it. EXP had lower effectiveness compared to other treatment options. The effectiveness of medical treatments was similar compared to surgery. Mixed evidence of low confidence suggests increased effectiveness for MIFE+MISO compared to MISO alone (RR 1.49, 95% CI: 1.09-2.03). Side effects were similar among all options. Fewer women needed analgesia following EVAC compared to MISO (RR for MISO 0.43, 95% CI: 0.27-0.68) and in the EXP group compared to EVAC (RR 2.07, 95% CI: 1.25-3.41). MVA had higher ranking (low likelihood) for post-treatment infection and serious complications (SUCRA 87.6 and 79.2%, respectively) with the highest likelihood for post-treatment satisfaction (SUCRA 98%). WIDER IMPLICATIONS: Medical treatments for first-trimester miscarriage have similar effectiveness and side effects compared to surgery. The addition of MIFE could increase the effectiveness of MISO and reduce side effects, although evidence is limited due to inconsistency. EXP has lower effectiveness compared to other treatment options.Systematic review registration: Prospero CRD42016048920.

Reported Outcomes in Perinatal Iron Deficiency Anemia Trials: A Systematic Review.

BACKGROUND/AIMS: Iron deficiency (ID) and iron deficiency anemia (IDA) are global health concerns associated with adverse perinatal effects. Despite efforts taken at the international level, there is no consensus on unified prevention/treatment strategies, largely stemming from inconsistencies of outcome reporting. Our objective was to comprehensively assess outcome reporting perinatal iron intervention trials as Phase 1 of core outcome set (COS) development to inform future research. METHODS: Systematic search in MEDLINE, EMBASE, Cochrane Databases, and CINAHL (January 2000 - April 2016), with inclusion of trials involving pregnant or postpartum women with ID/IDA confirmed before recruitment. Articles were independently screened and selected by 2 reviewers; data were extracted in duplicate. Quality was assessed using published scoring systems. Outcome definitions and measurement methods were tabulated. RESULTS: Of 7,046 citations, 33 randomized controlled trials were included. Sixty-nine reported outcomes were categorized into 8 domains. High methodological quality characterized 25 (76%) studies. Reporting quality was low in 16 (49%), moderate in 13 (39%), and high in 4 (12%) studies. Variation was greatest for outcome definition, timing of assessment and measurement methods. CONCLUSION: This review identifies a comprehensive long-list of outcomes reported of perinatal iron interventions for ID/IDA. Beyond highlighting existing variation in outcome reporting, it provides a foundation for development of a COS for future trials.

MRI versus laparoscopy to diagnose the main causes of chronic pelvic pain in women: a test-accuracy study and economic evaluation.

BACKGROUND: Chronic pelvic pain (CPP) symptoms in women are variable and non-specific; establishing a differential diagnosis can be hard. A diagnostic laparoscopy is often performed, although a prior magnetic resonance imaging (MRI) scan may beneficial. OBJECTIVES: To estimate the accuracy and added value of MRI in making diagnoses of (1) idiopathic CPP and (2) the main gynaecological causes of CPP. To quantify the impact MRI can have on decision-making with respect to triaging for therapeutic laparoscopy and to conduct an economic evaluation. DESIGN: Comparative test-accuracy study with cost-effectiveness modelling. SETTING: Twenty-six UK-based hospitals. PARTICIPANTS: A total of 291 women with CPP. METHODS: Pre-index information concerning the patient's medical history, previous pelvic examinations and ultrasound scans was collected. Women reported symptoms and quality of life at baseline and 6 months. MRI scans and diagnostic laparoscopy (undertaken and interpreted blind to each other) were the index tests. For each potential cause of CPP, gynaecologists indicated their level of certainty that the condition was causing the pelvic pain. The analysis considered both diagnostic laparoscopy as a reference standard for observing structural gynaecological causes and consensus from a two-stage expert independent panel for ascertaining the cause of CPP. The stage 1 consensus was based on pre-index, laparoscopy and follow-up data; for stage 2, the MRI scan report was also provided. The primary analysis involved calculations of sensitivity and specificity for the presence or absence of each structural gynaecological cause of pain. A decision-analytic model was developed, with a 6-month time horizon. Two strategies, laparoscopy or MRI, were considered and populated with study data. RESULTS: Using reference standards of laparoscopic and expert panel diagnoses, MRI scans had high specificity but poor sensitivity for observing deep-infiltrating endometriosis, endometrioma, adhesions and ovarian cysts. MRI scans correctly identified 56% [95% confidence interval (CI) 48% to 64%] of women judged to have idiopathic CPP, but missed 46% (95% CI 37% to 55%) of those considered to have a gynaecological structural cause of CPP. MRI added significant value, over and above the pre-index information, in identifying deep-infiltrating endometriosis (p = 0.006) and endometrioma (p = 0.02) as the cause of pain, but not for other gynaecological structural causes or for identifying idiopathic CPP (p = 0.08). Laparoscopy was significantly more accurate than MRI in diagnosing idiopathic CPP (p < 0.0001), superficial peritoneal endometriosis (p < 0.0001), deep-infiltrating endometriosis (p < 0.0001) and endometrioma of the ovary (p = 0.02) as the cause of pelvic pain. The accuracy of laparoscopy appeared to be able to rule in these diagnoses. Using MRI to identify women who require therapeutic laparoscopy would lead to 369 women in a cohort of 1000 receiving laparoscopy unnecessarily, and 136 women who required laparoscopy not receiving it. The economic analysis highlighted the importance of the time horizon, the prevalence of CPP and the cut-off values to inform the sensitivity and specificity of MRI and laparoscopy on the model results. MRI was not found to be a cost-effective diagnostic approach in any scenario. CONCLUSIONS: MRI was dominated by laparoscopy in differential diagnosis of women presenting to gynaecology clinics with CPP. It did not add value to information already gained from history, examination and ultrasound about idiopathic CPP and various gynaecological conditions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13028601. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 40. See the NIHR Journals Library website for further project information.

A randomised controlled trial and economic evaluation of intraoperative cell salvage during caesarean section in women at risk of haemorrhage: the SALVO (cell SALVage in Obstetrics) trial.

BACKGROUND: Caesarean section is associated with blood loss and maternal morbidity. Excessive blood loss requires transfusion of donor (allogeneic) blood, which is a finite resource. Cell salvage returns blood lost during surgery to the mother. It may avoid the need for donor blood transfusion, but reliable evidence of its effects is lacking. OBJECTIVES: To determine if routine use of cell salvage during caesarean section in mothers at risk of haemorrhage reduces the rates of blood transfusion and postpartum maternal morbidity, and is cost-effective, in comparison with standard practice without routine salvage use. DESIGN: Individually randomised controlled, multicentre trial with cost-effectiveness analysis. Treatment was not blinded. SETTING: A total of 26 UK obstetric units. PARTICIPANTS: Out of 3054 women recruited between June 2013 and April 2016, we randomly assigned 3028 women at risk of haemorrhage to cell salvage or routine care. Randomisation was stratified using random permuted blocks of variable sizes. Of these, 1672 had emergency and 1356 had elective caesareans. We excluded women for whom cell salvage or donor blood transfusion was contraindicated. INTERVENTIONS: Cell salvage (intervention) versus routine care without salvage (control). In the intervention group, salvage was set up in 95.6% of the women and, of these, 50.8% had salvaged blood returned. In the control group, 3.9% had salvage deployed. MAIN OUTCOME MEASURES: Primary - donor blood transfusion. Secondary - units of donor blood transfused, time to mobilisation, length of hospitalisation, mean fall in haemoglobin, fetomaternal haemorrhage (FMH) measured by Kleihauer-Betke test, and maternal fatigue. Analyses were adjusted for stratification factors and other factors that were believed to be prognostic a priori. Cost-effectiveness outcomes - costs of resources and service provision taking the UK NHS perspective. RESULTS: We analysed 1498 and 1492 participants in the intervention and control groups, respectively. Overall, the transfusion rate was 2.5% in the intervention group and 3.5% in the control group [adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42 to 1.01; p = 0.056]. In a planned subgroup analysis, the transfusion rate was 3.0% in the intervention group and 4.6% in the control group among emergency caesareans (adjusted OR 0.58, 95% CI 0.34 to 0.99), whereas it was 1.8% in the intervention group and 2.2% in the control group among elective caesareans (adjusted OR 0.83, 95% CI 0.38 to 1.83) (interaction p = 0.46, suggesting that the difference in effect between subgroups was not statistically significant). Secondary outcomes did not differ between groups, except for FMH, which was higher under salvage in rhesus D (RhD)-negative women with RhD-positive babies (25.6% vs. 10.5%, adjusted OR 5.63, 95% CI 1.43 to 22.14; p = 0.013). No case of amniotic fluid embolism was observed. The additional cost of routine cell salvage during caesarean was estimated, on average, at £8110 per donor blood transfusion avoided. CONCLUSIONS: The modest evidence for an effect of routine use of cell salvage during caesarean section on rates of donor blood transfusion was associated with increased FMH, which emphasises the need for adherence to guidance on anti-D prophylaxis. We are unable to comment on long-term antibody sensitisation effects. Based on the findings of this trial, cell salvage is unlikely to be considered cost-effective. FUTURE WORK: Research into risk of alloimmunisation among women exposed to cell salvage is needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN66118656. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 2. See the NIHR Journals Library website for further project information.

Variations in reporting of outcomes in randomized trials on diet and physical activity in pregnancy: A systematic review.

AIM: Trials on diet and physical activity in pregnancy report on various outcomes. We aimed to assess the variations in outcomes reported and their quality in trials on lifestyle interventions in pregnancy. METHODS: We searched major databases without language restrictions for randomized controlled trials on diet and physical activity-based interventions in pregnancy up to March 2015. Two independent reviewers undertook study selection and data extraction. We estimated the percentage of papers reporting 'critically important' and 'important' outcomes. We defined the quality of reporting as a proportion using a six-item questionnaire. Regression analysis was used to identify factors affecting this quality. RESULTS: Sixty-six randomized controlled trials were published in 78 papers (66 main, 12 secondary). Gestational diabetes (57.6%, 38/66), preterm birth (48.5%, 32/66) and cesarian section (60.6%, 40/66), were the commonly reported 'critically important' outcomes. Gestational weight gain (84.5%, 56/66) and birth weight (87.9%, 58/66) were reported in most papers, although not considered critically important. The median quality of reporting was 0.60 (interquartile range 0.25, 0.83) for a maximum score of one. Study and journal characteristics did not affect quality. CONCLUSION: Many studies on lifestyle interventions in pregnancy do not report critically important outcomes, highlighting the need for core outcome set development.

Diagnostic accuracy of Cancer Antigen 125 (CA125) for endometriosis in symptomatic women: A multi-center study.

STUDY OBJECTIVE: To assess the diagnostic accuracy of serum Cancer Antigen 125 (CA 125)≥30units/milliliter (u/ml) for diagnosing endometriosis in symptomatic women. STUDY DESIGN: Prospective observational cohort study including patients with symptoms of pelvic pain or subfertility undergoing elective diagnostic laparoscopy at two tertiary referral hospitals. We excluded patients suspected to have other gynecological pathology. We evaluated the accuracy of serum CA 125 (index test) with histologically confirmed endometriosis (reference standard). MAIN RESULTS: Fifty-eight consecutive women recruited between October 2013 to March 2015. Women with endometriosis had a higher CA 125 level than those without endometriosis (mean 54.7+/-71.6 vs 16.2+/- 8.0). The specificity of CA 125≥30u/ml was 96% (95% CI 81.7-99.9%) and sensitivity was 57% (95% CI 37.4-74.5%). The positive likelihood ratio for the histological presence of endometriosis with a CA 125≥30u/ml was 15.8 (95% CI 2.3-112) providing a post-test probability of 94% (95% CI 71%-99%) in women with pelvic pain or subfertility. The area under the curve, 0.85 (95% CI 0.74-0.96) indicates high test accuracy. CONCLUSIONS: CA 125≥30u/ml is highly predictive of endometriosis in women with symptoms of pain and/or subfertility. CA 125 should be considered as a rule-in test for expediting the diagnosis and management of endometriosis, CA 125 <30u/ml is, however, unable to rule out endometriosis.

Anaesthesia-related maternal mortality in low-income and middle-income countries: a systematic review and meta-analysis.

BACKGROUND: The risk factors contributing to maternal mortality from anaesthesia in low-income and middle-income countries and the burden of the problem have not been comprehensively studied up to now. We aimed to obtain precise estimates of anaesthesia-attributed deaths in pregnant women exposed to anaesthesia and to identify the factors linked to adverse outcomes in pregnant women exposed to anaesthesia in low-income and middle-income countries. METHODS: In this systematic review and meta-analysis, we searched major electronic databases from inception until Oct 1, 2015, for studies reporting risks of maternal death from anaesthesia in low-income and middle-income countries. Studies were included if they assessed maternal and perinatal outcomes in pregnant women exposed to anaesthesia for an obstetric procedure in countries categorised as low-income or middle-income by the World Bank. We excluded studies in high-income countries, those involving non-pregnant women, case reports, and studies published before 1990 to ensure that the estimates reflect the current burden of the condition. Two independent reviewers undertook quality assessment and data extraction. We computed odds ratios for risk factors and anaesthesia-related complications, and pooled them using a random effects model. This study is registered with PROSPERO, number CRD42015015805. FINDINGS: 44 studies (632,556 pregnancies) reported risks of death from anaesthesia in women who had an obstetric surgical procedure; 95 (32,149,636 pregnancies and 36,144 deaths) provided rates of anaesthesia-attributed deaths as a proportion of maternal deaths. The risk of death from anaesthesia in women undergoing obstetric procedures was 1·2 per 1000 women undergoing obstetric procedures (95% CI 0·8-1·7, I(2)=83%). Anaesthesia accounted for 2·8% (2·4-3·4, I(2)=75%) of all maternal deaths, 3·5% (2·9-4·3, I(2)=79%) of direct maternal deaths (ie, those that resulted from obstetric complications), and 13·8% (9·0-20·7, I(2)=84%) of deaths after caesarean section. Exposure to general anaesthesia increased the odds of maternal (odds ratio [OR] 3·3, 95% CI 1·2-9·0, I(2)=58%), and perinatal deaths (2·3, 1·2-4·1, I(2)=73%) compared with neuraxial anaesthesia. The rate of any maternal death was 9·8 per 1000 anaesthetics (5·2-15·7, I(2)=92%) when managed by non-physician anaesthetists compared with 5·2 per 1000 (0·9-12·6, I(2)=95%) when managed by physician anaesthetists. INTERPRETATION: The current international priority on strengthening health systems should address the risk factors such as general anaesthesia and rural setting for improving anaesthetic care in pregnant women. FUNDING: Ammalife Charity and ELLY Appeal, Bart's Charity.

Type 1 and Type 2 Diabetes Preconception and in Pregnancy: Health Impacts, Influence of Obesity and Lifestyle, and Principles of Management.

Preexisting diabetes in pregnancy results in increased risks to the mother, fetus, and neonate. Preconception care is vital to reduce risk of miscarriage, congenital malformations, and perinatal mortality. Preconception care should empower women with realistic goal setting, healthy lifestyle, and diabetes self-management skills, to ensure a positive experience of the pregnancy and to reduce diabetes-related distress. In high-risk women without known diabetes, preconception and early antenatal screening is crucial to enable prompt treatment of hyperglycemia and any complications. The prevalence of obesity in reproductive age women is rising, further increasing risk of poor pregnancy outcomes in women with diabetes. Adverse lifestyle factors should be addressed preconception and in the antenatal period, allowing opportunity to improve physical health, manage weight, and improve neonatal outcomes. Management of diabetes in pregnancy involves individualized and intensified insulin therapy, accounting for expected changes in insulin sensitivity, and minimizing glucose variability and hypoglycemia. Diabetes complications must be screened for and managed as necessary. Delivery timing will depend on fetal surveillance and obstetric considerations. It is important to maintain engagement and motivation of these women in the postpartum period, encouraging breastfeeding and postpartum weight management and supporting diabetes management.

Non-anaemic iron deficiency - a disease looking for recognition of diagnosis: a systematic review.

OBJECTIVE: To capture all data meeting a rigid definition of non-anaemic iron deficiency (NAID) and determine whether it is associated with poor outcomes compared with normal iron status and whether iron supplementation improves outcomes in NAID. DESIGN: Systematic review. DATA SOURCES: EMBASE, Medline, Web of Science, clinicaltrials.gov, International Clinical Trials Registry Platform (ICTRP) and Central from database inception to April 2014. ELIGIBILITY CRITERIA: Ferritin <16 µg/L (<12 µg/L if age <5 yr) in the absence of anaemia in observational studies or randomised trials. Where populations were deemed to be sufficiently similar, meta-analysis was undertaken. RESULTS: There were 21 studies included. NAID in pregnancy associated with reduction in birthweight (P = 0.028). Iron supplementation in NAID was associated with improvement in objective scores (P = 0.005) and self-rating (P = 0.03) of fatigue. Meta-analysis was limited and, where possible, was not statistically significant including the comparison of NAID with cardiovascular function in adults (VO2max P = 0.21, RERmax P = 0.68), educational attainment in children (P = 0.14), infant mental (P = 0.29) and psychomotor (P = 0.07) development, and iron supplementation in NAID with educational attainment in language (P = 0.31). CONCLUSIONS: There is emerging evidence that NAID is a disease in its own right, deserving of further research in the development of strategies for detection and treatment.