Implications of fetal premature atrial contractions: systematic review.

OBJECTIVE: Fetal heart-rate irregularities occur in 1-2% of pregnancies and are usually caused by premature atrial contractions (PAC). Although PAC are considered benign, they may be associated with cardiac defects and tachyarrhythmia. We aimed to determine the incidence of congenital heart defects (CHDs) and complications in fetuses with PAC. METHODS: This was a systematic review and meta-analysis conducted in accordance with the PRISMA statement for reporting items for systematic reviews and meta-analyses. MEDLINE and EMBASE were searched from 1990 to June 2021 to identify studies on fetuses with PAC. The primary outcome was CHD; secondary outcomes were complications using the endpoints supraventricular tachyarrhythmia (SVT), cardiac failure and intrauterine fetal demise. Meta-analysis of proportions was performed, subdivided into high-risk and low-risk populations based on reason for referral. Pooled incidences with 95% CIs were calculated. RESULTS: Of 2443 unique articles identified, 19 cohort studies including 2260 fetuses were included. The pooled incidence of CHD in fetuses with PAC was 2.8% (95% CI, 1.5-4.1%), when 0.6% is the incidence expected in the general population. The pooled incidence of CHD was 7.2% (95% CI, 3.5-10.9%) in the high-risk population and 0.9% (95% CI, 0.0-2.0%) in the low-risk population. SVT occurred in 1.4% (95% CI, 0.6-3.4%) of fetuses diagnosed with PAC. Cardiac failure was described in 16 fetuses (1.4% (95% CI, 0.5-3.5%)), of which eight were CHD-related. Intrauterine fetal demise occurred in four fetuses (0.9% (95% CI, 0.5-1.7%)) and was related to CHD in two cases. CONCLUSIONS: Our findings suggest that the risk of CHD in fetuses with PAC is 4-5 times higher than that in the general population. CHD was present more frequently in the high-risk population. Consequently, an advanced ultrasound examination to diagnose PAC correctly and exclude CHD is recommended. Complications of PAC are rare but can result in fetal demise, thus weekly fetal heart-rate monitoring remains advisable to enable early detection of SVT and to prevent cardiac failure. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The long-term effect of prenatal progesterone treatment on child development, behaviour and health: a systematic review.

BACKGROUND: Progesterone is widely used in prenatal care. However, long-term effects of prenatal progesterone treatment on child development are unclear. OBJECTIVES: To evaluate long-term outcomes in children after prenatal progesterone treatment. SEARCH STRATEGY: MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to 24 May 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) reporting outcomes in children born to women who received progesterone treatment (compared with placebo or another intervention) during any trimester in pregnancy. DATA COLLECTION AND ANALYSIS: Two authors independently selected and extracted data. We used the Cochrane Risk of Bias tool for randomised trials and Quality In Prognosis Studies. MAIN RESULTS: Of 388 papers, we included seven articles based on five RCTs, comprising 4222 measurements of children aged 6 months to 8 years. All studies compared progesterone to placebo in second and/or third trimester for the prevention of preterm birth. Meta-analysis (two studies, n = 890 children) showed no difference in neurodevelopment as assessed by the Bayley-III Cognitive Composite score at 2 years between children exposed to progesterone versus placebo (Standardised Mean Difference -0.04, 95% Confidence Interval -0.26 to 0.19), I2  = 22%. Heterogeneity prohibited additional meta-analyses. Other long-term outcomes showed no differences. CONCLUSIONS: Our systematic review comprising a multitude of developmental measurements with a broad age range did not find evidence of benefit or harm in offspring prenatally exposed to progesterone treatment for the prevention of preterm birth. We identified an urgent need for follow-up studies of prenatal progesterone administration in early pregnancy and effects in offspring beyond early childhood. TWEETABLE ABSTRACT: Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear.

Novel imaging techniques to study postmortem human fetal anatomy: a systematic review on microfocus-CT and ultra-high-field MRI.

BACKGROUND: MRI and CT have been extensively used to study fetal anatomy for research and diagnostic purposes, enabling minimally invasive autopsy and giving insight in human fetal development. Novel (contrast-enhanced) microfocus CT (micro-CT) and ultra-high-field (≥ 7.0 T) MRI (UHF-MRI) techniques now enable micron-level resolution that combats the disadvantages of low-field MRI and conventional CT. Thereby, they might be suitable to study fetal anatomy in high detail and, in time, contribute to the postmortem diagnosis of fetal conditions. OBJECTIVES: (1) To systematically examine the usability of micro-CT and UHF-MRI to study postmortem human fetal anatomy, and (2) to analyze factors that govern success at each step of the specimen preparation and imaging. METHOD: MEDLINE and EMBASE were systematically searched to identify publications on fetal imaging by micro-CT or UHF-MRI. Scanning protocols were summarized and best practices concerning specimen preparation and imaging were enumerated. RESULTS: Thirty-two publications reporting on micro-CT and UHF-MRI were included. The majority of the publications focused on imaging organs separately and seven publications focused on whole body imaging, demonstrating the possibility of visualization of small anatomical structures with a resolution well below 100 µm. When imaging soft tissues by micro-CT, the fetus should be stained by immersion in Lugol's staining solution. CONCLUSION: Micro-CT and UHF-MRI are both excellent imaging techniques to provide detailed images of gross anatomy of human fetuses. The present study offers an overview of the current best practices when using micro-CT and/or UHF-MRI to study fetal anatomy for clinical and research purposes. KEY POINTS: • Micro-CT and UHF-MRI can both be used to study postmortem human fetal anatomy for clinical and research purposes. • Micro-CT enables high-resolution imaging of fetal specimens in relatively short scanning time. However, tissue staining using a contrast solution is necessary to enable soft-tissue visualization. • UHF-MRI enables high-resolution imaging of fetal specimens, without the necessity of prior staining, but with the drawback of long scanning time.

European Position Paper on Rhinosinusitis and Nasal Polyps 2020.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Preoperative frailty parameters as predictors for outcomes after transcatheter aortic valve implantation: a systematic review and meta-analysis.

Guidelines suggest using frailty characteristics in the work-up for a transcatheter aortic valve implantation (TAVI). There are many frailty-screening tools with different components. The prognostic value of the individual parameters in frailty is as yet unclear. The objective of this systematic review and meta-analysis was to find and pool predictors for 1­year mortality after TAVI. We followed a two-step approach. First, we searched for randomised controlled trials on TAVI to identify frailty parameters used in these studies. Second, we searched for publications on these frailty parameters. Articles were included for pooled analysis if the studied frailty parameters were dichotomised with clear cut-off values based on common standards or clinical practice and reported adjusted hazard ratios (HR) of 1­year mortality after TAVI. We calculated pooled effect estimates of 49 studies based on dichotomised frailty scores (HR: 2.16, 95% CI: 1.57-3.00), chronic lung disease (HR: 1.57, 95% CI: 1.45-1.70), estimated glomerular filtration rate <30 ml/min (HR: 1.95, 95% CI: 1.68-2.29), body mass index <20 kg/m2 (HR: 1.49, 95% CI: 1.09-2.03), hypoalbuminaemia (HR: 1.77, 95% CI: 1.38-2.25), anaemia (HR: 2.08, 95% CI: 0.93-4.66), low gait speed (HR: 13.33, 95% CI: 1.75-101.49) and Katz activities of daily living (ADL) score of 1 or more deficits (HR: 5.16, 95% CI: 0.77-34.47). Chronic lung disease, chronic kidney disease, underweight, hypoalbuminaemia, a low frailty score, anaemia, low gait speed and an ADL deficiency were associated with worse 1­year outcomes after TAVI.

The pathophysiology of the septate uterus: a systematic review.

BACKGROUND: Little is known about the pathophysiology underlying the increased risk for impaired reproductive outcomes in women with a septate uterus. OBJECTIVES: We explored the available evidence on the pathophysiology of the septate uterus in an attempt to find a biological basis for these effects. SEARCH STRATEGY: We performed a systematic literature search in OVID MEDLINE and OVID EMBASE from inception to January 2018. SELECTION CRITERIA: We selected studies that investigated the pathophysiology of the septate uterus. Case reports or reviews without original data were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently evaluated potentially eligible papers. MAIN RESULTS: Thirty-eight studies were included for analysis. The overall findings were that the intrauterine septum consists of endometrium and myometrium similar to the uterine wall. All five imaging studies that evaluated vascularity found that most of the intrauterine septa were vascularised. Histological studies found that the intrauterine septum consisted of myometrium and was covered by endometrium (n = 9). The endometrium covering the septum showed differences in histological composition in four studies and in gene expression in three studies compared with the normal uterine wall. CONCLUSIONS: We found no clear biological basis for the impaired reproductive outcomes in women with a septate uterus. Either the gross anatomy of the septum itself or differences in histology or gene expression of the septum could account for the increased risk of reproductive waste observed after implantation in the septum. TWEETABLE ABSTRACT: In women with a septate uterus differences in histology or gene expression could account for impaired reproductive outcome.

Vaginal delivery in women with a low-lying placenta: a systematic review and meta-analysis.

BACKGROUND: Low-lying placentas are positioned close to the internal os of the cervix. The preferred way of delivery within this group is unclear. OBJECTIVES: To review the literature on the success of a vaginal delivery with a low-lying placenta. SEARCH STRATEGY: We searched OVID EMBASE and MEDLINE for studies on vaginal delivery with a low-lying placenta. DATA COLLECTION AND ANALYSES: Data was extracted on successful vaginal delivery and emergency caesarean section due to haemorrhage. We distinguished between different distances between the cervical os and the placenta (internal os distance, IOD); 0-10, 11-20, and >20 mm. A meta-analysis of proportions was made for successful vaginal delivery and emergency caesarean section at every cut-off value. Maternal morbidity (i.e. antepartum blood loss, postpartum haemorrhage and blood transfusion) at different cut-off values was evaluated. MAIN RESULTS: Of the 999 articles retrieved, 10 articles met our inclusion criteria. A vaginal delivery was successful at an IOD of 0-10 mm in 43%, at an IOD of 11-20 mm in 85%, and at an IOD of >20 mm in 82%. A shorter IOD had a higher chance of antepartum haemorrhage, whereas a larger IOD needed postpartum blood transfusion more often. Postpartum haemorrhage did not depend on IOD. CONCLUSION: A low-lying placenta is not a contraindication for a trial of labour, and the morbidity in these women is not increased. However, women with a low-lying placenta have a higher chance of an emergency caesarean section compared with women with a placenta outside the lower uterine segment. Therefore, shared decision-making is mandatory in case of a trial of labour. TWEETABLE ABSTRACT: This systematic review demonstrates the possibility of a vaginal delivery in women with a low-lying placenta within 20 mm of the cervix.

EPOS2020: development strategy and goals for the latest European Position Paper on Rhinosinusitis.

BACKGROUND: The European Position Papers on Rhinosinusitis from 2005, 2007 and 2012 have had a measurable impact on the way this common condition with high impact on quality of life is managed around the world. EPOS2020 will be the latest iteration of the guideline, addressing new stakeholders and target users, presenting a summary of the latest literature and evolving treatment modalities, and formulating clear recommendations based on all available evidence. METHODOLOGY: Based on the AGREE II framework, this article demonstrates how the EPOS2020 steering group will address six key areas to ensure consistency in quality and presentation of information in the latest rhinosinusitis clinical practice guideline: scope and purpose; stakeholder involvement; rigour of development; clarity of presentation; recommendations and applicability; editorial independence. RESULTS: By analysing the guidance from AGREE II, we formulated a detailed development strategy for EPOS2020. We identify new stakeholders and target users and ratify the importance of patient involvement in the latest EPOS guideline. New and expanded areas of research to be addressed are highlighted. We confirm our intention to use mixed methodologies, combining evidence-based medicine with real life studies; when no evidence can be found, use Delphi rounds to achieve clear, inclusive recommendations. We also introduce new concepts for dissemination of the guideline, using Internet and social media to improve accessibility. CONCLUSION: This article is an introduction to the EPOS2020 project, and presents the key goals, core stakeholders, planned methodology and dissemination strategies for the latest version of this influential guideline.

Laser treatment of congenital melanocytic naevi: a systematic review.

Recent studies on congenital melanocytic naevi (CMN) indicate a lower risk of melanoma than has been previously assumed. As a result, the treatment paradigm in CMN has shifted from complete removal to cosmetically acceptable, less invasive treatment options, such as laser treatment. Our objective was to review systematically the efficacy and safety of laser therapy for CMN. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and PubMed. We rated the quality of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Twenty-four eligible studies (three nonrandomized controlled studies; 21 case series) with 434 patients were included; the majority were of poor quality). Twenty different laser modalities or combinations were evaluated. Overall, the Q-switched laser was used most frequently, although large or giant CMN were generally treated with an ablative laser. Owing to heterogeneity between studies, comparison between laser modalities was hampered and statistical analysis was precluded. Lasers in CMN showed rather good results (albeit with very low-quality evidence) for clearing of hyperpigmentation in the short term. Outcome measures varied widely, patient satisfaction was rarely measured and high incidences of scarring, repigmentation and complications were reported. No malignant change was seen. While most studies report short-term improvement of CMN after laser therapy, there is no high-quality evidence for the efficacy and safety of laser modalities in CMN in the long term. Future research should focus on well-conducted and well-reported prospective studies on different laser modalities for CMN, with the use of recognized and validated outcome measures.

Variation in hyperemesis gravidarum definition and outcome reporting in randomised clinical trials: a systematic review.

BACKGROUND: Hyperemesis gravidarum (HG) is a common cause of hospital admission in early pregnancy. There is no international consensus on the definition of HG, or on outcomes that should be reported in trials. Consistency in definition and outcome reporting is important for the interpretation and synthesis of data in meta-analyses. OBJECTIVE: To identify which HG definitions and outcomes are currently in use in trials. SEARCH STRATEGY: We searched the following sources: (1) Cochrane Central Register of Controlled Trials, (2) Embase and (3) Medline for published trials and the WHO-ICTRP database for ongoing trials (27 October 2017). SELECTION CRITERIA: All randomised clinical trials reporting on any intervention for HG were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and extracted data on HG definition and outcomes. MAIN RESULTS: We included 31 published trials reporting data from 2511 women and three ongoing trials with a planned sample size of 360 participants. We identified 11 definition items. Most commonly used definition items were vomiting (34 trials) and nausea (30 trials). We identified 34 distinct outcomes. Most commonly reported outcomes were vomiting (29 trials), nausea (26 trials), need for hospital treatment (14 trials) and duration of hospital (re)admission(s) (14 trials). CONCLUSION: There is substantial variation of HG definition and outcome reporting in trials. This hampers meaningful aggregation of trial results in meta-analysis and implementation of evidence in guidelines. To overcome this, international consensus on a definition and a core outcome set for HG trials should be developed. TWEETABLE ABSTRACT: There is a wide variation of definitions and outcomes reported in trials on hyperemesis gravidarum.

CTCA for detection of significant coronary artery disease in routine TAVI work-up : A systematic review and meta-analysis.

Transcatheter aortic valve implantation (TAVI) has evolved to standard treatment of severe aortic stenosis in patients with an intermediate to high surgical risk. Computed tomography coronary angiography (CTCA) could partially replace invasive coronary angiography to diagnose significant coronary artery disease in the work-up for TAVI. A literature search was performed in MEDLINE and EMBASE for papers comparing CTCA and coronary angiography in TAVI candidates. The primary endpoint was the diagnostic accuracy of CTCA, compared to coronary angiography, for detection of significant (>50% diameter stenosis) coronary artery disease, measured as sensitivity, specificity, positive-(PPV) and negative predictive value (NPV). Seven studies were included, with a cumulative sample size of 1,275 patients. The patient-based pooled sensitivity, specificity, PPV and NPV were 95, 65, 71 and 94% respectively. Quality assessment revealed excellent and good quality in terms of applicability and risk of bias respectively, with the main concern being patient selection. In conclusion, on the basis of a significance cut-off value of 50% diameter stenosis, CTCA provides acceptable diagnostic accuracy for the exclusion of coronary artery disease in patients referred for TAVI. Using the routinely performed preoperative computed tomography scans as a gatekeeper for coronary angiography could decrease additional coronary angiographies by 37% in this high-risk and fragile population.

Selective outcome reporting and sponsorship in randomized controlled trials in IVF and ICSI.

STUDY QUESTION: Are randomized controlled trials (RCTs) on IVF and ICSI subject to selective outcome reporting and is this related to sponsorship? SUMMARY ANSWER: There are inconsistencies, independent from sponsorship, in the reporting of primary outcome measures in the majority of IVF and ICSI trials, indicating selective outcome reporting. WHAT IS KNOWN ALREADY: RCTs are subject to bias at various levels. Of these biases, selective outcome reporting is particularly relevant to IVF and ICSI trials since there is a wide variety of outcome measures to choose from. An established cause of reporting bias is sponsorship. It is, at present, unknown whether RCTs in IVF/ICSI are subject to selective outcome reporting and whether this is related with sponsorship. STUDY DESIGN, SIZE, DURATION: We systematically searched RCTs on IVF and ICSI published between January 2009 and March 2016 in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and the publisher subset of PubMed. We analysed 415 RCTs. PARTICIPANTS/MATERIALS, SETTING, METHODS: Per included RCT, we extracted data on impact factor of the journal, sample size, power calculation, and trial registry and thereafter data on primary outcome measure, the direction of trial results and sponsorship. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 415 identified RCTs, 235 were excluded for our primary analysis, because the sponsorship was not reported. Of the 180 RCTs included in our analysis, 7 trials did not report on any primary outcome measure and 107 of the remaining 173 trials (62%) reported on surrogate primary outcome measures. Of the 114 registered trials, 21 trials (18%) provided primary outcomes in their manuscript that were different from those in the trial registry. This indicates selective outcome reporting. We found no association between selective outcome reporting and sponsorship. We ran additional analyses to include the trials that had not reported sponsorship and found no outcomes that differed from our primary analysis. LIMITATIONS, REASONS FOR CAUTION: Since the majority of the trials did not report on sponsorship, there is a risk on sampling bias. WIDER IMPLICATIONS OF THE FINDINGS: IVF and ICSI trials are subject, to a large extent, to selective outcome reporting. Readers should be aware of this to avoid implementation of false or misleading results in clinical practice. STUDY FUNDING/COMPETING INTERESTS: No funding received and there are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Endometrial thickness in women undergoing IUI with ovarian stimulation. How thick is too thin? A systematic review and meta-analysis.

STUDY QUESTION: Is pre-ovulatory endometrial thickness (EMT) in women with unexplained subfertility undergoing IUI with ovarian stimulation (OS) associated with pregnancy chances? SUMMARY ANSWER: We found no evidence for an association between EMT and pregnancy chances. WHAT IS KNOWN ALREADY: It has been suggested that OS with clomiphene citrate (CC) results in a lower EMT than with gonadotrophins or aromatase inhibitors, but the clinical consequences in terms of pregnancy are unclear. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and meta-analysis of studies comparing CC, gonadotrophins or aromatase inhibitors in an IUI program reporting on EMT and pregnancy rates in women with unexplained subfertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched MEDLINE, EMBASE and the non-MEDLINE subset of PubMed from inception to 28th June 2016 and cross-checked references of relevant articles. Outcome measures were clinical pregnancy rate and mean pre-ovulatory EMT. We calculated mean differences (MD) with 95% CIs with a fixed effect model, and in case of heterogeneity with an I2 > 50% a random effect model. We performed a meta-regression analysis to determine if stimulating drugs interacted with the estimated effect of EMT. MAIN RESULTS AND THE ROLE OF CHANCE: Our search retrieved 1563 articles of which 23 were included, totaling 3846 women. There were 17 RCTs and 6 cohort studies. The average study quality was low and there was considerable to substantial statistical heterogeneity. Seven studies provided data on EMT in relation to pregnancy. There was no evidence of a difference in EMT between women who conceived and women that did not conceive (1525 women, MDrandom: 0.51 mm, 95% CI: -0.05 to 1.07). Women treated with CC had a significantly thinner EMT than women treated with gonadotrophins (two studies, MD: -0.33, 95% CI: -0.64 to -0.01). There was no evidence of a difference in EMT when comparing CC with letrozole (five studies, MDrandom: -0.84, 95% CI: -1.97 to 0.28). The combination of CC plus gonadotrophins resulted in a slightly thinner endometrium than letrozole (nine studies, MDrandom: -0.79, 95% CI: -1.37 to -0.20). Letrozole resulted in a thinner EMT than gonadotrophins (two studies, MDrandom: -1.31, 95% CI: -2.08 to -0.53). LIMITATIONS, REASONS FOR CAUTION: The overall quality of the included studies was low to moderate. We found considerable to substantial heterogeneity in the comparisons, hampering firm conclusions. WIDER IMPLICATIONS OF THE FINDINGS: We found no evidence for an association between EMT and pregnancy rates during IUI -OS. As a consequence, canceling IUI cycles because of a thin endometrial lining may negatively affect clinical care. Although we found some evidence for very small differences in EMT when comparing various drugs, we cannot make inferences on their effect on pregnancy chances since these differences may be coincidental. STUDY FUNDING/COMPETING INTEREST(S): None. REGISTRATION NUMBER: N/A.

Evaluation of the measurement properties of symptom measurement instruments for atopic eczema: a systematic review.

BACKGROUND: Symptoms have been identified as a core outcome domain for atopic eczema (AE) trials. Various instruments exist to measure symptoms in AE, but they vary in quality and there is a lack of standardization between clinical trials. Our objective was to systematically evaluate the quality of the evidence on the measurement properties of AE symptom instruments, thereby informing consensus discussions within the Harmonising Outcome Measures for Eczema (HOME) initiative regarding the most appropriate instruments for the core outcome domain symptoms. METHODS: Using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and predefined criteria for good measurement properties on identified development and validation studies of AE symptom instruments, a best evidence synthesis was performed to draw an overall conclusion on quality of the instruments and to provide recommendations. RESULTS: Eighteen instruments were identified and evaluated. When the quality and results of the studies were considered, only five of these instruments had sufficient validation data to consider them for the core outcome set for the core outcome domain symptoms. These were the paediatric Itch Severity Scale (ISS), Patient-Oriented Eczema Measure (POEM), Patient-Oriented SCOring Atopic Dermatitis (PO-SCORAD), Self-Administered Eczema Area and Severity Index (SA-EASI) and adapted SA-EASI. CONCLUSIONS: ISS (paediatric version), POEM, PO-SCORAD, SA-EASI and adapted SA-EASI are currently the most appropriate instruments and therefore have the potential to be recommended as core symptom instrument in future clinical trials. These findings will be utilized for the development of a core outcome set for AE.

How to write a Critically Appraised Topic: evidence to underpin routine clinical practice.

Critically appraised topics (CATs) are essential tools for busy clinicians who wish to ensure that their daily clinical practice is underpinned by evidence-based medicine. CATs are short summaries of the most up-to-date, high-quality available evidence that is found using thorough structured methods. They can be used to answer specific, patient-orientated questions that arise recurrently in real-life practice. This article provides readers with a detailed guide to performing their own CATs. It is split into four main sections reflecting the four main steps involved in performing a CAT: formulation of a focused question, a search for the most relevant and highest-quality evidence, critical appraisal of the evidence and application of the results back to the patient scenario. As well as helping to improve patient care on an individual basis by answering specific clinical questions that arise, CATs can help spread and share knowledge with colleagues on an international level through publication in the evidence-based dermatology section of the British Journal of Dermatology.

Dilatation and curettage increases the risk of subsequent preterm birth: a systematic review and meta-analysis.

STUDY QUESTION: Could dilatation and curettage (D&C), used in the treatment of miscarriage and termination of pregnancy, increase the risk of subsequent preterm birth? SUMMARY ANSWER: A history of curettage in women is associated with an increased risk of preterm birth in a subsequent pregnancy compared with women without such history. WHAT IS KNOWN ALREADY: D&C is one of the most frequently performed procedures in obstetrics and gynaecology. Apart from the acknowledged but relatively rare adverse effects, such as cervical tears, bleeding, infection, perforation of the uterus, bowel or bladder, or Asherman syndrome, D&C has been suggested to also lead to an increased risk of preterm birth in the subsequent pregnancy. STUDY DESIGN, SIZE, DURATION: In the absence of randomized data, we conducted a systematic review and meta-analysis of cohort and case-control studies. PARTICIPANTS/MATERIALS, SETTING, METHODS: We searched OVID MEDLINE and OVID EMBASE form inception until 21 May 2014. We selected cohort and case-control studies comparing subsequent preterm birth in women who had a D&C for first trimester miscarriage or termination of pregnancy and a control group of women without a history of D&C. MAIN RESULTS AND THE ROLE OF CHANCE: We included 21 studies reporting on 1 853 017 women. In women with a history of D&C compared with those with no such history, the odds ratio (OR) for preterm birth <37 weeks was 1.29 (95% CI 1.17; 1.42), while for very preterm birth the ORs were 1.69 (95% CI 1.20; 2.38) for <32 weeks and 1.68 (95% CI 1.47; 1.92) for <28 weeks. The risk remained increased when the control group was limited to women with a medically managed miscarriage or induced abortion (OR 1.19, 95% CI 1.10; 1.28). For women with a history of multiple D&Cs compared with those with no D&C, the OR for preterm birth (<37 weeks) was 1.74 (95% CI 1.10; 2.76). For spontaneous preterm birth, the OR was 1.44 (95% CI 1.22; 1.69) for a history of D&C compared with no such history. LIMITATIONS, REASONS FOR CAUTION: There were no randomized controlled trials comparing women with and without a history of D&C and subsequent preterm birth. As a consequence, confounding may be present since the included studies were either cohort or case-control studies, not all of which corrected the results for possible confounding factors. WIDER IMPLICATIONS OF THE FINDINGS: This meta-analysis shows that D&C is associated with an increased risk of subsequent preterm birth. The increased risk in association with multiple D&Cs indicates a causal relationship. Despite the fact that confounding cannot be excluded, these data warrant caution in the use of D&C for miscarriage and termination of pregnancy, the more so since less invasive options are available. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066.

Incidence of and risk indicators for vasa praevia: a systematic review.

BACKGROUND: Vasa praevia (VP) is a rare phenomenon that is assumed to increase the risk of severe complications, including fetal death. Critical data on its incidence are lacking, so there is no rational basis for prenatal screening. OBJECTIVES: To review the literature on the incidence and risk indicators for VP. SEARCH STRATEGY: We searched OVID MEDLINE, OVID EMBASE, the Cochrane Library and PubMed for case-control and cohort studies on incidence and risk indicators for VP. SELECTION CRITERIA: Two reviewers selected studies and scored their methodological quality. DATA COLLECTION AND ANALYSIS: We calculated the mean incidence of VP. We constructed 2 × 2 tables cross-classifying potential risk indicators against the incidence of VP to calculate common odds ratios and 95% confidence intervals, using the Mantel-Haenszel method. MAIN RESULTS: We included 13 studies (two prospective cohort studies, ten retrospective cohort studies and one case-control study) reporting on 569 410 patients with 325 cases of VP. Based on ten included cohort studies providing information on the incidence, the mean incidence of VP was 0.60 per 1000 pregnancies. We identified five different risk indicators and markers for VP: second-trimester placenta praevia, conception by assisted reproductive technologies, a bilobed or succenturiate placenta, umbilical cord insertion in the lower third part of the uterus at first-trimester ultrasound and velamentous cord insertion. Almost 83% of the cases of VP had one or more risk indicators. AUTHORS' CONCLUSIONS: In view of the low incidence, screening for VP in an unselected population is not advised. Targeted screening of women with one or more risk indicators as a part of routine mid-gestation scanning should be considered. TWEETABLE ABSTRACT: Vasa praevia is more common in placenta praevia, conception by ART, velamentous cord insertion and bilobed placenta.

Diphenylcyclopropenone in patients with alopecia areata. A critically appraised topic.

AIM: To assess the efficacy and safety of topical diphenylcyclopropenone (DPCP) in patients with alopecia areata. SETTING AND DESIGN: Study selection, data extraction, risk of bias assessment and analyses were carried out independently by two authors. The quality of evidence was rated with Grading of Recommendations Assessment, Development and Evaluation (GRADE). No randomised trials were identified, but 11 case series, conducted in dermatology departments in the Netherlands, UK, Iran, Italy, Egypt and Greece were included. STUDY EXPOSURE: Patients with mainly extensive and long-lasting alopecia totalis and universalis were treated. Most often one side of the scalp was treated with DPCP whilst the other side received no treatment. Treatment duration varied from 4 to 48 months with a follow up of 6 to 36 months. OUTCOMES: Outcomes included quality of life, patient satisfaction, adverse events, treatment effect and duration of remission. RESULTS: Eleven studies, with sample sizes of 18-139 comprising 500 patients, were retrieved. Our critical outcomes quality of life and patient satisfaction, were not or hardly addressed. In about half of the patients DPCP appeared to be effective, with transient side effects such as contact eczema, blistering, oedema of eyelids, headache and flu-like symptoms. If treatment was satisfactory the effect was maintained for more than a year. The overall quality of the evidence was rated very low. CONCLUSION: There is very low quality evidence for the effectiveness and safety in extensive resistant alopecia areata. Well-designed and well-conducted randomised controlled trials, with subsequent adequate reporting, including high-quality descriptions of all aspects of methodology are required.

Systematic review of accuracy of ultrasound in the diagnosis of vasa previa.

OBJECTIVE: Vasa previa is an obstetric complication in which the fetal blood vessels lie outside the chorionic plate in close proximity to the internal cervical os. In women with vasa previa, the risk of rupture of these vessels is increased, thus potentially causing fetal death or serious morbidity. Our objective was to assess the accuracy of ultrasound in the prenatal diagnosis of vasa previa. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and PubMed for studies on vasa previa. Two reviewers independently selected studies on the accuracy of ultrasound in the diagnosis of vasa previa. The studies were scored on methodological quality using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). Data on sensitivity and specificity were subsequently extracted. RESULTS: The literature search revealed 583 articles, of which two prospective and six retrospective cohort studies were eligible for inclusion in the qualitative analysis. All studies documented methods suitable for the prenatal diagnosis of vasa previa. Four out of the eight studies used transvaginal ultrasound (TVS) for primary evaluation, while the remaining four studies used transabdominal ultrasound and performed a subsequent TVS when vasa previa was suspected. The QUADAS-2 tool reflected poor methodology in six of the eight included studies, and prenatal detection rates varied from 53% (10/19) to 100% (total of 442,633 patients, including 138 cases of vasa previa). In the two prospective studies (n = 33,795, including 11 cases of vasa previa), transvaginal color Doppler performed during the second trimester detected all cases of vasa previa (sensitivity, 100%) with a specificity of 99.0-99.8%. CONCLUSION: The accuracy of ultrasound in the diagnosis of vasa previa is high when performed transvaginally in combination with color Doppler.

Assessment of vaginal atrophy: a review.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to provide an evidence-based definition of vaginal atrophy (VA) and present an overview of subjective and objective measurements of VA applicable in clinical practice and research. METHODS: A systematic literature search was performed in MEDLINE and EMBASE to identify studies reporting on measurement properties of diagnostic instruments for VA. Additional searches in MEDLINE aimed to document the definitions, diagnostic criteria, and outcome measures of VA. Studies reporting on definitions, diagnosis, outcome measurements, and measurement properties of diagnostic instruments of VA were selected. RESULTS: Specific symptoms for VA that were consistently described could be identified to suggest an evidence-based definition of VA. As subjective outcome measurements, seven scoring systems to assess the signs of VA during physical examination were identified. The most bothersome symptom (MBS) approach is most useful in clinical practice and research as it focuses on the most common symptoms of VA. As objective outcome measurements, numerous ways to assess vaginal cytology and vaginal pH were identified. CONCLUSIONS: At the moment, there is no consensus on the definition and assessment of VA. We propose to define VA as a common manifestation of estrogen decline associated with specific symptoms of which the most common are: vaginal dryness, itching or irritation, and dyspareunia. In both clinical and research settings, subjective assessment (the MBS approach) and objective assessments of VA (measurement of vaginal maturation index and vaginal pH) should be combined.