Service evaluation of an early pregnancy loss support clinic in an inner London early pregnancy unit.

BACKGROUND: Early pregnancy loss (EPL) can have profound implications for physical and psychological health. In the UK, significant variation in service provision exists for women affected by EPL. There is very little guidance on what hospital-based follow-up support services should entail, and how these can be implemented and integrated into current care provision to meet the needs of women who experience EPL. This service evaluation (SE) reports on an Early Pregnancy Loss Support Clinic (EPLSC) in an inner-city Hospital Trust. METHODS: This SE gathered both quantitative and qualitative feedback from women to assess the value of a locally implemented Early Pregnancy Loss Support Clinic (EPLSC). Quantitative feedback was collected using the Short Assessment of Patient Satisfaction (SAPS) questionnaire and the Visual Anxiety Scale (VAS-A), both administered to women attending the EPLSC. Qualitative feedback was collected through semi-structured interviews and focused on four pre-determined themes based on EPL literature - physical health, mental health, role of the bereavement midwife and overall service user experience. Quantitative feedback was summarised using descriptive statistics, while qualitative feedback was analysed using framework analysis. RESULTS: A total of 127 women were invited to the EPLSC, with 110 (87%) attending, and 17 (13%) not attending their appointment. SAPS scores ranged from 21 to 28, indicating that women were either satisfied or very satisfied with the care they received at the EPLSC. Results from VAS-A scores showed that 76 (69%) women reported a decrease in anxiety immediately after attending the EPLSC, compared to 8 (7%) who reported no change or a small increase in anxiety. Qualitative findings highlighted women's concerns around future fertility, the importance of emotional support and the value of connecting with the bereavement midwife. CONCLUSION: An EPLSC that focuses on providing emotional support and reassurance, particularly regarding future fertility, is important to women. Further rigorous evaluation of national disparities in EPL follow-up is urgently needed to assess the gaps in clinical care delivery.

Evaluating cut-off levels for progesterone, ß human chorionic gonadotropin and ß human chorionic gonadotropin ratio to exclude pregnancy viability in women with a pregnancy of unknown location: A prospective multicenter cohort study.

INTRODUCTION: There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and ß human chorionic gonadotropin (ßhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, ßhCG, and ßhCG ratio cut-off levels to exclude a VIUP in women with a pregnancy of unknown location. MATERIAL AND METHODS: This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial ßhCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14 weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non-viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut-off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, ßhCG, and ßhCG ratio. RESULTS: Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for ßhCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had ßhCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59 nmol/L, VIUP were identified with levels as low as 5 nmol/L. No single ßhCG cut-off reliably ruled out the presence of viability with certainty, even when the level was more than 3000 IU/L, there were 39/358 (11%) women who had a VIUP. The probability of viability decreases with the ßhCG ratio. Although the median ßhCG ratio associated with viability was 2.26, VIUP were identified with ratios as low as 1.02. A progesterone level below 2 nmol/L and ßhCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation. CONCLUSIONS: Cut-off levels for ßhCG, ßhCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although ßhCG ratio and progesterone have slightly better performance in comparison, single ßhCG used in this manner is highly unreliable.

Systematic review of immunoglobulin use in paediatric neurological and neurodevelopmental disorders.

AIM: A systematic literature review of intravenous immunoglobulin (IVIG) treatment of paediatric neurological conditions was performed to summarize the evidence, provide recommendations, and suggest future research. METHOD: A MEDLINE search for articles reporting on IVIG treatment of paediatric neuroinflammatory, neurodevelopmental, and neurodegenerative conditions published before September 2015, excluding single case reports and those not in English. Owing to heterogeneous outcome measures, meta-analysis was not possible. Findings were combined and evidence graded. RESULTS: Sixty-five studies were analysed. IVIG reduces recovery time in Guillain-Barré syndrome (grade B). IVIG is as effective as corticosteroids in chronic inflammatory demyelinating polyradiculoneuropathy (grade C), and as effective as tacrolimus in Rasmussen syndrome (grade C). IVIG improves recovery in acute disseminated encephalomyelitis (grade C), reduces mortality in acute encephalitis syndrome with myocarditis (grade C), and improves function and stabilizes disease in myasthenia gravis (grade C). IVIG improves outcome in N-methyl-d-aspartate receptor encephalitis (grade C) and opsoclonus-myoclonus syndrome (grade C), reduces cataplexy symptoms in narcolepsy (grade C), speeds recovery in Sydenham chorea (grade C), reduces tics in selected cases of Tourette syndrome (grade D), and improves symptoms in paediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (grade B). INTERPRETATION: IVIG is a useful therapy in selected neurological conditions. Well-designed, prospective, multi-centre studies with standardized outcome measures are required to compare treatments.

Do women with pain and bleeding in early pregnancy require a vaginal speculum examination as part of their assessment?

AIMS: To investigate whether a vaginal speculum examination (VSE) prior to a transvaginal scan (TVS) alters the diagnosis or management of women who complain of bleeding in early pregnancy. METHODS: A prospective study. Women were asked to describe their bleeding as heavy, moderate or light and to consent to VSE prior to TVS. TVS was performed to obtain a final diagnosis of pregnancy outcome. RESULTS: 221 consecutive women were included in the study. In 14.5% (n = 32) complaining of heavy bleeding, blood was seen in all but two VSE and 84% (n = 27) had a miscarriage diagnosed by TVS. Products of conception were removed in 18.8% (n = 6), but this did not alter the subsequent immediate management of any cases. 65.2% (n = 144) of women complained of light bleeding, blood was seen on VSE in 53% (n = 77). Of these women, 25% (n = 19) of those where blood was seen had a miscarriage, compared to 6% (n = 4) of women where blood was not seen. A cervical ectropion was visualised in 11.7% (n = 26) and 2.3% (n = 5) had a cervical polyp. No other clinically significant pathology was detected. CONCLUSION: The amount of bleeding reported by women in early pregnancy relates well with VSE findings. Performing a VSE did not alter the subsequent management of these patients. This study demonstrates that routine objective assessment of blood by a clinician performing VSE prior to a TVS is unnecessary.

Accurate prediction of pregnancy viability by means of a simple scoring system.

STUDY QUESTION: What is the performance of a simple scoring system to predict whether women will have an ongoing viable intrauterine pregnancy beyond the first trimester? SUMMARY ANSWER: A simple scoring system using demographic and initial ultrasound variables accurately predicts pregnancy viability beyond the first trimester with an area under the curve (AUC) in a receiver operating characteristic curve of 0.924 [95% confidence interval (CI) 0.900-0.947] on an independent test set. WHAT IS KNOWN ALREADY: Individual demographic and ultrasound factors, such as maternal age, vaginal bleeding and gestational sac size, are strong predictors of miscarriage. Previous mathematical models have combined individual risk factors with reasonable performance. A simple scoring system derived from a mathematical model that can be easily implemented in clinical practice has not previously been described for the prediction of ongoing viability. STUDY DESIGN, SIZE AND DURATION: This was a prospective observational study in a single early pregnancy assessment centre during a 9-month period. PARTICIPANTS/MATERIALS, SETTING AND METHODS: A cohort of 1881 consecutive women undergoing transvaginal ultrasound scan at a gestational age <84 days were included. Women were excluded if the first trimester outcome was not known. Demographic features, symptoms and ultrasound variables were tested for their influence on ongoing viability. Logistic regression was used to determine the influence on first trimester viability from demographics and symptoms alone, ultrasound findings alone and then from all the variables combined. Each model was developed on a training data set, and a simple scoring system was derived from this. This scoring system was tested on an independent test data set. MAIN RESULTS AND THE ROLE OF CHANCE: The final outcome based on a total of 1435 participants was an ongoing viable pregnancy in 885 (61.7%) and early pregnancy loss in 550 (38.3%) women. The scoring system using significant demographic variables alone (maternal age and amount of bleeding) to predict ongoing viability gave an AUC of 0.724 (95% CI = 0.692-0.756) in the training set and 0.729 (95% CI = 0.684-0.774) in the test set. The scoring system using significant ultrasound variables alone (mean gestation sac diameter, mean yolk sac diameter and the presence of fetal heart beat) gave an AUC of 0.873 (95% CI = 0.850-0.897) and 0.900 (95% CI = 0.871-0.928) in the training and the test sets, respectively. The final scoring system using demographic and ultrasound variables together gave an AUC of 0.901 (95% CI = 0.881-0.920) and 0.924 (CI = 0.900-0.947) in the training and the test sets, respectively. After defining the cut-off at which the sensitivity is 0.90 on the training set, this model performed with a sensitivity of 0.92, specificity of 0.73, positive predictive value of 84.7% and negative predictive value of 85.4% in the test set. LIMITATIONS, REASONS FOR CAUTION: BMI and smoking variables were a potential omission in the data collection and might further improve the model performance if included. A further limitation is the absence of information on either bleeding or pain in 18% of women. Caution should be exercised before implementation of this scoring system prior to further external validation studies WIDER IMPLICATIONS OF THE FINDINGS: This simple scoring system incorporates readily available data that are routinely collected in clinical practice and does not rely on complex data entry. As such it could, unlike most mathematical models, be easily incorporated into normal early pregnancy care, where women may appreciate an individualized calculation of the likelihood of ongoing pregnancy viability. STUDY FUNDING/COMPETING INTEREST(S): Research by V.V.B. supported by Research Council KUL: GOA MaNet, PFV/10/002 (OPTEC), several PhD/postdoc & fellow grants; IWT: TBM070706-IOTA3, PhD Grants; IBBT; Belgian Federal Science Policy Office: IUAP P7/(DYSCO, `Dynamical systems, control and optimization', 2012-2017). T.B. is supported by the Imperial Healthcare NHS Trust NIHR Biomedical Research Centre. TRIAL REGISTRATION NUMBER: Not applicable.

Ultrasound in the diagnosis of ectopic pregnancy.

The majority of ectopic pregnancies can be diagnosed on transvaginal scan before treatment. Diagnosis should be based on positive visualization of an ectopic pregnancy rather the inability to visualize an intrauterine pregnancy. The majority of ectopic pregnancies will be visible on the initial transvaginal scan performed. Those who do not have their ectopic pregnancies visualized on the first examination will be initially classified as having a pregnancy of unknown location. They will then need follow-up until a diagnosis of ectopic pregnancy is confirmed. This review discusses the use of ultrasound in the diagnosis of ectopic pregnancy and the specific criteria for diagnosis of the different types of ectopic pregnancy.

The risk of venous thromboembolism in early pregnancy loss: Review of the literature and current guidelines and the need for guidance - Communication from the SSC on Women's Health Issues for thrombosis and haemostasis.

BACKGROUND: Thromboembolic disease is one of the major causes of mortality and morbidity in pregnancy and the puerperium, with 1 death per 100 000 births attributed to venous thromboembolism (VTE). Factors associated with development of thrombosis are all present in pregnancy, with some of these changes seen from conception. OBJECTIVE: Given how common early pregnancy loss is, the aim of this review is to evaluate the uncertainty surrounding the risk of VTE following early pregnancy loss and termination of pregnancy. METHODS: A structured literature search was conducted to identify existing evidence as well as international pregnancy-specific guidelines regarding assessment and prevention of VTE risk in pregnant women. This review was reviewed, critiqued, and approved by all members of the International Society on Thrombosis and Haemostasis subcommittee for Women's Health Issues in Thrombosis and Haemostasis. RESULTS: Four published original research studies, one clinical comment paper, and six guidelines were reviewed. Despite clear evidence of the increased risk of VTE in pregnancy, there is a lack of guidance regarding evaluation and management after early pregnancy loss. CONCLUSION: International collaborative research to determine the risk of VTE and its prevention in women undergoing surgical termination of pregnancy or following surgical management of early pregnancy loss is urgently needed. Pregnancy-specific risk assessment taking into account preexisting risk factors is advocated. Education of health care professionals involved in early pregnancy care and guidance on management, albeit based on limited existing evidence, are necessary to highlight the need for individualized care.

Ectopic pregnancy: using the hCG ratio to select women for expectant or medical management.

OBJECTIVE: To identify variables that can be used to select women with an ectopic pregnancy for expectant or medical management with systemic methotrexate. DESIGN: Cohort study. SETTING: Early Pregnancy Unit of a London teaching hospital. POPULATION: Women with a tubal ectopic pregnancy managed non-surgically. METHODS: The diagnosis of tubal ectopic pregnancy was made using transvaginal sonography. Human chorionic gonadotrophin (hCG) levels had to be taken at 0 hour and 48 hours pre-treatment. Other recorded variables include presenting complaints, gestational age, progesterone levels, size of the ectopic mass and appearance of the ectopic on transvaginal sonography. Women were followed up until the outcome (success or failure) of management was known. MAIN OUTCOME MEASURES: Univariable analysis was performed to identify the variables associated with successful management using area under curves and relative risks. RESULTS: Thirty-nine women underwent expectant management (overall success rate 71.8%) and 42 had medical management (overall success rate 76.2%). The pre-treatment hCG ratio (hCG 48 hours/hCG 0 hour) was related to the failure of both expectant (area under curve 0.86, 95% CI 0.67-0.94) and medical (area under curve 0.79, 95% CI 0.58-0.90) management. History of ectopic pregnancy was related to failure of expectant management only (relative risk 0.46, 95% CI 0.16-0.92). CONCLUSIONS: The most important variable for predicting the likelihood of successful non-surgical management was the pre-treatment hCG ratio. New studies are required to validate the use of this variable and of history of ectopic pregnancy to predict the likelihood of successful non-surgical management in clinical practice.

Is serum human chorionic gonadotrophin follow-up necessary after suspected spillage of trophoblast at the time of laparoscopic surgery for ectopic pregnancy?

BACKGROUND: Persistent trophoblast is a recognised complication of salpingostomy for the treatment of ectopic pregnancy, with reported rates of 3-20%; hence, women are advised to have serum human chorionic gonadotrophin (hCG) levels monitored post-operatively. Although much less common, there are also reports of disseminated trophoblastic peritoneal implants after laparoscopic salpingectomy. The aim of this study was to assess whether monitoring of post-operative serum hCG levels is necessary in women undergoing salpingectomy, where intra-operative spillage of trophoblast is thought to have occurred. METHODS: This was a retrospective study of women who underwent serum hCG follow-up after salpingectomy. Serum hCG levels were monitored if: (1) the ectopic pregnancy was found to be ruptured; (2) there was a significant haemoperitoneum (>500 ml); (3) there was thought to be spillage of trophoblast at the time of salpingectomy or (4) a tubal miscarriage was diagnosed. Serum hCG levels were taken at days 1-2, days 3-4, days 6-8 or days 13-15 post-surgery. Women were followed up until the serum hCG level was <15 IU/l. Persistent trophoblast was defined as a failure of the serum hCG level to decrease spontaneously after surgery. RESULTS: 105 women underwent serum hCG follow-up after a laparoscopy for a tubal ectopic pregnancy. Of these women, 92 had a laparoscopic salpingectomy and 13 were diagnosed with a tubal miscarriage at the time of laparoscopy. In all women the serum hCG decreased spontaneously. CONCLUSION: It does not appear necessary to routinely monitor serum hCG levels post-operatively in women diagnosed with tubal miscarriages, in those undergoing salpingectomy for a ruptured ectopic pregnancy or in cases of salpingectomy, where there is thought to be spillage of trophoblast.

Recurrent pregnancy loss: diagnostic workup after two or three pregnancy losses? A systematic review of the literature and meta-analysis.

BACKGROUND: Recurrent pregnancy loss (RPL) occurs in 1-3% of all couples trying to conceive. No consensus exists regarding when to perform testing for risk factors in couples with RPL. Some guidelines recommend testing if a patient has had two pregnancy losses whereas others advise to test after three losses. OBJECTIVE AND RATIONALE: The aim of this systematic review was to evaluate the current evidence on the prevalence of abnormal test results for RPL amongst patients with two versus three or more pregnancy losses. We also aimed to contribute to the debate regarding whether the investigations for RPL should take place after two or three or more pregnancy losses. SEARCH METHODS: Relevant studies were identified by a systematic search in OVID Medline and EMBASE from inception to March 2019. A search for RPL was combined with a broad search for terms indicative of number of pregnancy losses, screening/testing for pregnancy loss or the prevalence of known risk factors. Meta-analyses were performed in case of adequate clinical and statistical homogeneity. The quality of the studies was assessed using the Newcastle-Ottawa scale. OUTCOMES: From a total of 1985 identified publications, 21 were included in this systematic review and 19 were suitable for meta-analyses. For uterine abnormalities (seven studies, odds ratio (OR) 1.00, 95% CI 0.79-1.27, I2 = 0%) and for antiphospholipid syndrome (three studies, OR 1.04, 95% CI 0.86-1.25, I2 = 0%) we found low quality evidence for a lack of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses. We found insufficient evidence of a difference in prevalence of abnormal test results between couples with two versus three or more pregnancy losses for chromosomal abnormalities (10 studies, OR 0.78, 95% CI 0.55-1.10), inherited thrombophilia (five studies) and thyroid disorders (two studies, OR 0.52, 95% CI: 0.06-4.56). WIDER IMPLICATIONS: A difference in prevalence in uterine abnormalities and antiphospholipid syndrome is unlikely in women with two versus three pregnancy losses. We cannot exclude a difference in prevalence of chromosomal abnormalities, inherited thrombophilia and thyroid disorders following testing after two versus three pregnancy losses. The results of this systematic review may support investigations after two pregnancy losses in couples with RPL, but it should be stressed that additional studies of the prognostic value of test results used in the RPL population are urgently needed. An evidenced-based treatment is not currently available in the majority of cases when abnormal test results are present.

Terminology for describing normally sited and ectopic pregnancies on ultrasound: ESHRE recommendations for good practice.

STUDY QUESTION: What recommendations can be provided to improve terminology for normal and ectopic pregnancy description on ultrasound? SUMMARY ANSWER: The present ESHRE document provides 17 consensus recommendations on how to describe normally sited and different types of ectopic pregnancies on ultrasound. WHAT IS KNOWN ALREADY: Current diagnostic criteria stipulate that each type of ectopic pregnancy can be defined by clear anatomical landmarks which facilitates reaching a correct diagnosis. However, a clear definition of normally sited pregnancies and a comprehensive classification of ectopic pregnancies are still lacking. STUDY DESIGN SIZE DURATION: A working group of members of the ESHRE Special Interest Group in Implantation and Early Pregnancy (SIG-IEP) and selected experts in ultrasound was formed in order to write recommendations on the classification of ectopic pregnancies. PARTICIPANTS/MATERIALS SETTING METHODS: The working group included nine members of different nationalities with internationally recognised experience in ultrasound and diagnosis of ectopic pregnancies on ultrasound. This document is developed according to the manual for development of ESHRE recommendations for good practice. The recommendations were discussed until consensus by the working group, supported by a survey among the members of the ESHRE SIG-IEP. MAIN RESULTS AND THE ROLE OF CHANCE: A clear definition of normally sited pregnancy on ultrasound scan is important to avoid misdiagnosis of uterine ectopic pregnancies. A comprehensive classification of ectopic pregnancy must include definitions and descriptions of each type of ectopic pregnancy. Only a classification which provides descriptions and diagnostic criteria for all possible locations of ectopic pregnancy would be fit for use in routine clinical practice. The working group formulated 17 recommendations on the diagnosis of the different types of ectopic pregnancies on ultrasound. In addition, for each of the types of ectopic pregnancy, a schematic representation and examples on 2D and 3D ultrasound are provided. LIMITATIONS REASONS FOR CAUTION: Owing to the limited evidence available, recommendations are mostly based on clinical and technical expertise. WIDER IMPLICATIONS OF THE FINDINGS: This document is expected to have a significant impact on clinical practice in ultrasound for early pregnancy. The development of this terminology will help to reduce the risk of misdiagnosis and inappropriate treatment. STUDY FUNDING/COMPETING INTERESTS: The meetings of the working group were funded by ESHRE. T.T. declares speakers' fees from GE Healthcare. The other authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A. DISCLAIMER: This Good Practice Recommendations (GPR) document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation. ESHRE's GPRs should be used for informational and educational purposes. They should not be interpreted as setting a standard of care or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. Furthermore, ESHRE's GPRs do not constitute or imply the endorsement, recommendation or favouring of any of the included technologies by ESHRE.

Assessing first trimester growth: the influence of ethnic background and maternal age.

BACKGROUND: First trimester growth restriction may predict miscarriage or adverse outcome later in the pregnancy, but determinants of early growth are not well described. Our objective was to examine factors influencing fetal and gestational sac size in the first trimester. METHODS: Prospective observational study of 1828 singleton pregnancies before 12 weeks gestation. Maternal characteristics (ethnicity, maternal age, obstetric history, abdominal pain and vaginal bleeding), crown rump length (CRL) and mean gestational sac diameter (MSD) were recorded. A stepwise linear mixed effects analysis was performed to determine factors influencing rate of change in CRL and MSD. RESULTS: 1063 scans, in 464 women, were included. Rate of increase in CRL was higher in women of black ethnic origin (P = 0.0261) compared with white, and increased with advancing maternal age (P = 0.0046). Maternal age also influenced MSD: older women had gestational sacs which were 0.118 mm larger for each one year increase in maternal age (P = 0.0073). Bleeding, pain and prior obstetric history did not influence CRL or MSD. CONCLUSIONS: Rate of increase in CRL was greater in fetuses of black versus white women and increased with advancing maternal age. As CRL is used to date pregnancies, and this influences further growth assessment, consideration should be given to the use of individualized growth charts which take account of maternal factors found to influence first trimester growth.

The use of serum inhibin A and activin A levels in predicting the outcome of 'pregnancies of unknown location'.

BACKGROUND: The aim was to evaluate the role of serum inhibin A and activin A in the prediction of the outcome of women with 'pregnancies of unknown location' (PULs). METHODS: Serum human chorionic gonadotrophin (hCG), progesterone, inhibin A and activin A levels were measured at 0 and 48 h. Differences in the mean levels and the change in levels over 48 h expressed as a ratio (48/0 h) were examined between the three outcome groups--failing PUL, intrauterine pregnancy (IUP) or ectopic pregnancy. Variables were incorporated into logistic regression models to predict the pregnancy outcomes, which were evaluated using receiver operator characteristic curves. RESULTS: One hundred and forty-one women were classified as PULs: 67 failing PULs (47.5%), 58 IUPs (41.1%) and 16 ectopic pregnancies (11.4%). Activin A levels were not significantly different between the three outcome groups. Inhibin A levels were significantly lower in failing PULs. The logistic regression model based on serum inhibin levels gave an area under the curve (AUC) of 0.88 for failing PUL, 0.87 for IUP and 0.60 for ectopic pregnancy. The model based on serum activin levels gave an AUC of 0.61 for failing PUL, 0.64 for IUP and 0.51 for ectopic pregnancy, and the model based on serum hCG levels gave an AUC of 0.95 for failing PUL, 0.97 for IUP and 0.67 for ectopic pregnancy. CONCLUSIONS: Serum activin A levels at 0 and 48 h are not helpful in predicting the outcome of PULs. Although serum inhibin A levels may be of use in the prediction of failing PULs and IUPs in the PUL populations, they do not perform as well as serum hCG levels.

The hCG ratio can predict the ultimate viability of the intrauterine pregnancies of uncertain viability in the pregnancy of unknown location population.

BACKGROUND: To determine whether hCG ratio at 48 h can predict ultimate viability of intrauterine pregnancies of uncertain viability (IPUVs) in the pregnancy of unknown location (PUL) population. METHODS: Prospective observational study from June 2001 to October 2004. All women classified with PUL had serum hCG levels measured at 0 and 48 h to calculate hCG ratio (hCG 48/hCG 0 h). All women were followed up until final diagnosis: failing PUL, viable and non-viable intrauterine pregnancy (IUP), ectopic pregnancy. Those PULs found to have an IPUV at follow-up transvaginal ultrasound scan (TVS) were included in final analysis. RESULTS: During the study period, 12,572 consecutive first trimester women were scanned. One thousand and three (8%) women were classified PULs. Three hundred and seventy-nine (37.8%) PULs were confirmed IPUVs at follow-up scan. Complete data from 334 IPUVs were analyzed: 82.6% (276/334) viable IUPs and 17.4% (58/334) non-viable IUPs. Median hCG ratio was greater in viable IUPs [2.32, inter-quartile range (IQR) 1.16-4.77] compared with non-viable IUPs 1.83 (IQR 0.97-4.60). Sensitivity, specificity, positive and negative predictive value, positive and negative likelihood ratios of an hCG ratio >2.00 for the prediction of a viable IUP are 77.2%, 95.8%, 86.6%, 90.9%, 15.5, 0.24, respectively. In our population, an hCG ratio >2.00 increases the odds for a viable IUP from 0.42 to 6.46 post-test. CONCLUSIONS: The hCG ratio is significantly higher in those IPUVs which become viable IUPs compared with non-viable IUPs. New cut-offs for the hCG ratio need to be evaluated for the prediction of viability in the IPUV group of PULs.

Why are some ectopic pregnancies characterized as pregnancies of unknown location at the initial transvaginal ultrasound examination?

OBJECTIVE: To compare the appearance and behavior of ectopic pregnancies (EPs) initially classified as pregnancies of unknown location (PULs) to those visualized on the initial transvaginal ultrasound scan (TVS). METHODS: An observational study over a four-year period on women undergoing a TVS prior to diagnosis of a tubal EP. Demographic details, presenting symptoms, TVS findings, serum hCG and progesterone levels were recorded at the time of the initial TVS and at the time of diagnosis of the EP in those initially classified as a PUL. RESULTS: 411 women with a tubal EP underwent a TVS prior to treatment. In 85.9% (353/411) the EP was visualized on the initial TVS while 14.1%(58/411) were initially classified as PULs. Those initially classified as PULs had significantly lower mean gestational age and mean initial human chorionic gonadotrophin (hCG) levels, and significantly higher mean progesterone level at presentation than those where the EP was visualized on the initial TVS. Of those with a PUL, 60.3% (35/58) had the EP subsequently visualized on TVS. At the time of diagnosis these EPs were significantly smaller (p<0.0001); the appearance of the EPs, serum hCG and progesterone levels at the time of visualization on TVS were not significantly different from those visualized on the initial TVS. CONCLUSION: In women with EPs who are initially classified as PULs, failure of visualization of the EP on the initial TVS is likely to be due to the fact that they are too small and probably too early in the disease process.

Chlamydia trachomatis infection in patients attending an Early Pregnancy Unit: prevalence, symptoms, pregnancy location and viability.

OBJECTIVE: To assess the prevalence of Chlamydia trachomatis and its relationship to age, ethnicity, symptomatology, pregnancy location and viability in women attending an Early Pregnancy Unit. METHOD: Women were offered screening for Chlamydia over a 4-month period. Presenting complaints, maternal age, ethnic origin, gestational age, pregnancy location, pregnancy viability and swab results were recorded. RESULTS: One thousand, one hundred and one women were offered screening. Nine hundred and sixteen (83.2%) agreed to participate. Eight hundred and six (88.0%) had readable swabs. The prevalence of Chlamydia was 2.2% (95% CI: 1.4-3.5) (18/806). The prevalence in those <25 years of age was 8.7% (95% CI: 5.1-14.3). Prevalence was higher in black women compared to Asian or Caucasian women. The prevalence of Chlamydia in symptomatic and asymptomatic women was 2.3% (12/521) and 2.1% (6/285), respectively, p>0.166. There was no significant difference in the final early pregnancy outcome in women with or without Chlamydia. CONCLUSION: Currently Chlamydia screening is not advised in Early Pregnancy Units as the women are thought to be of low risk; however, there are subgroups that are at relatively high risk. Screening this population is therefore important. There is, however, no difference in pregnancy location and viability in women with or without Chlamydia.

Validation and updating of risk models based on multinomial logistic regression.

BACKGROUND: Risk models often perform poorly at external validation in terms of discrimination or calibration. Updating methods are needed to improve performance of multinomial logistic regression models for risk prediction. METHODS: We consider simple and more refined updating approaches to extend previously proposed methods for dichotomous outcomes. These include model recalibration (adjustment of intercept and/or slope), revision (re-estimation of individual model coefficients), and extension (revision with additional markers). We suggest a closed testing procedure to assist in deciding on the updating complexity. These methods are demonstrated on a case study of women with pregnancies of unknown location (PUL). A previously developed risk model predicts the probability that a PUL is a failed, intra-uterine, or ectopic pregnancy. We validated and updated this model on more recent patients from the development setting (temporal updating; n = 1422) and on patients from a different hospital (geographical updating; n = 873). Internal validation of updated models was performed through bootstrap resampling. RESULTS: Contrary to dichotomous models, we noted that recalibration can also affect discrimination for multinomial risk models. If the number of outcome categories is higher than the number of variables, logistic recalibration is obsolete because straightforward model refitting does not require the estimation of more parameters. Although recalibration strongly improved performance in the case study, the closed testing procedure selected model revision. Further, revision of functional form of continuous predictors had a positive effect on discrimination, whereas penalized estimation of changes in model coefficients was beneficial for calibration. CONCLUSIONS: Methods for updating of multinomial risk models are now available to improve predictions in new settings. A closed testing procedure is helpful to decide whether revision is preferred over recalibration. Because multicategory outcomes increase the number of parameters to be estimated, we recommend full model revision only when the sample size for each outcome category is large.

Facilitators and barriers to remaining at home for people with dementia who live alone: a protocol for a systematic review of qualitative evidence.

REVIEW QUESTION/OBJECTIVE: This qualitative review aims to gain an increased understanding of the factors that support (facilitators) and challenge (barriers) people who have dementia and live alone in being able to remain living in their own homes. The review will contribute to the development of a complex intervention, inform clinical practice and influence policy development for this population.Overarching review question: what are the barriers to, and facilitators for, people with a dementia who live alone being able to remain in their own homes? SUB-QUESTIONS: 1. What are the factors that support and/or challenge a person with dementia who lives alone?2. What are the barriers to, and facilitators for, people with a dementia who live alone being able to remain in their own homes from the perspective of people who have dementia and live alone?3. What are the barriers to, and facilitators for, people with dementia who live alone being able to remain in their own homes from the perspective of people who interact closely with this population, including family, and health and social care workers?