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Background: The relation between Chlamydia trachomatis infection and subsequent tubal damage is widely recognized. As such, C. trachomatis antibody (CAT) testing can be used to triage women for immediate tubal testing with hysterosalpingography (HSG) or laparoscopy. However, once invasive tubal testing has ruled out tubal pathology, CAT serology status is ignored, as its clinical significance is currently unknown. This study aimed to determine whether positive CAT serology is associated with lower spontaneous pregnancy rates in women in whom HSG and/or diagnostic laparoscopy showed no visible tubal pathology., Methods: We studied ovulatory women in whom HSG or laparoscopy showed patent tubes. Women were tested for C. trachomatis immunoglobulin G (IgG) antibodies with either micro-immunofluorescence (MIF) or an ELISA. CAT serology was positive if the MIF titre was ≥ 1:32 or if the ELISA index was >1.1. The proportion of couples pregnant without treatment was estimated at 12 months of follow-up. Time to pregnancy was considered censored at the date of the last contact when the woman was not pregnant or at the start of treatment. The association between CAT positivity and an ongoing pregnancy was evaluated with Cox regression analyses., Results: Of the 1882 included women without visible tubal pathology, 338 (18%) had a treatment-independent pregnancy within 1 year [estimated cumulative pregnancy rate 31%; 95% confidence interval (CI): 27-35%]. Because of differential censoring after 9 months of follow-up, regression analyses were limited to the first 9 months after tubal testing. Positive C. trachomatis IgG serology was associated with a statistically significant 33% lower probability of an ongoing pregnancy [adjusted fecundity rate ratio 0.66 (95% CI 0.49-0.89)]., Conclusions: Even after HSG or laparoscopy has shown no visible tubal pathology, subfertile women with a positive CAT have lower pregnancy chances than CAT negative women. After external validation, this finding could be incorporated into existing prognostic models.

Purpose: Transvaginal cervical length measurement in women with symptoms of preterm labor has been used to decide if treatment is necessary. Cervical length measurement may also have additional effects on patients, such as providing reassurance, although the evidence to support this is unclear. We explored and summarized to what extent additional effects of cervical length measurement in women with threatened preterm labor have been reported in the clinical literature and what the magnitude of these effects was., Methods: We performed a systematic review of the literature to identify articles reporting on cervical length measurements in women with symptoms of preterm labor. We assessed whether these articles reported patient outcomes other than preterm delivery., Results: The electronic and hand search resulted in 764 articles, of which 172 met initial criteria for further eligibility assessment. We found 12 articles that reported additional effects of cervical length measurement in symptomatic women, such as the reassurance or the sensory consequences related to the transvaginal procedure. None of the articles quantified such additional effects., Conclusions: There appears to be a gap between the presumed effects of cervical length measurement on patient outcomes, such as patients' reassurance, and the actual assessment of these effects during test evaluations. We suggest that future evaluations of prognostic preterm labor tests include a comprehensive assessment of patient outcomes.

Objectives: To review the literature on cervical length as a predictor of preterm birth in asymptomatic women with a multiple pregnancy., Methods: We searched MEDLINE, Embase and reference lists of included articles to identify all studies that reported on the accuracy of cervical length for predicting preterm birth in asymptomatic women with a multiple pregnancy. We scored study characteristics and study quality, and extracted data in order to construct two-by-two tables cross-classifying cervical length and preterm delivery. Meta-analysis using a bivariate model was performed. Summary receiver-operating characteristics (ROC) curves were generated for various test characteristics and outcome definitions., Results: We found 21 studies reporting on 2757 women. There was a large variation in gestational age at measurement, cut-off point for cervical length and definition of preterm birth. The summary ROC curve indicated a good predictive capacity of short cervical length for preterm birth. Summary estimates of sensitivity and specificity for preterm birth before 34 weeks' gestation were 78% and 66%, respectively, for 35 mm, 41% and 87% for 30 mm, 36% and 94% for 25 mm and 30% and 94% for 20 mm., Conclusions: In women with a multiple pregnancy, second-trimester cervical length is a strong predictor of preterm birth. In the absence of effective preventive strategies, there is currently no place in clinical practice for cervical length measurement in this population. However, future studies should evaluate preventive interventions in women with multiple pregnancies and a short cervix, and cervical length should be measured in any trial studying preventive strategies in multiple pregnancies., (Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.)

Objective: To assess the cost-effectiveness of addition of ST analysis of the fetal electrocardiogram (ECG; STAN) to cardiotocography (CTG) for fetal surveillance during labor compared with CTG only., Design: Cost-effectiveness analysis based on a randomized clinical trial on ST analysis of the fetal ECG., Setting: Obstetric departments of three academic and six general hospitals in The Netherlands. Population. Laboring women with a singleton high-risk pregnancy, a fetus in cephalic presentation, a gestational age >36 weeks and an indication for internal electronic fetal monitoring., Methods: A trial-based cost-effectiveness analysis was performed from a health-care provider perspective., Main Outcome Measures: Primary health outcome was the incidence of metabolic acidosis measured in the umbilical artery. Direct medical costs were estimated from start of labor to childbirth. Cost-effectiveness was expressed as costs to prevent one case of metabolic acidosis., Results: The incidence of metabolic acidosis was 0.7% in the ST-analysis group and 1.0% in the CTG-only group (relative risk 0.70; 95% confidence interval 0.38-1.28). Per delivery, the mean costs per patient of CTG plus ST analysis (n= 2 827) were €1,345 vs. €1,316 for CTG only (n= 2 840), with a mean difference of €29 (95% confidence interval -€9 to €77) until childbirth. The incremental costs of ST analysis to prevent one case of metabolic acidosis were €9 667., Conclusions: The additional costs of monitoring by ST analysis of the fetal ECG are very limited when compared with monitoring by CTG only and very low compared with the total costs of delivery., (© 2011 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2011 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: Many obstetric interventions are performed to improve long-term neonatal outcome. However, long-term neonatal outcome is usually not a primary outcome because it is time-consuming and expensive. The aim of this project was to identify different perinatal risk indicators and to develop prediction models for neurologic morbidity at 2 and 5 years of age., Study Design: Data from a Dutch cohort study of preterm and small-for-gestational-age infants was used. Neonates who were born in The Netherlands in 1983 with a gestational age of <34 weeks and without congenital abnormalities were included (n = 753). Infants were divided in 3 groups: no handicap, minor handicap, and major handicap., Results: Common risk indicators for major handicaps at 2 and 5 years of age were male sex (odds ratio, 2.7 and 3.0, respectively), seizures after ≥2 days of life (odds ratio, 5.8 and 5.8, respectively), and intracranial hemorrhage (odds ratio, 3.8 and 2.6, respectively)., Conclusion: In this cohort, male sex, intracranial hemorrhage, and seizures seem to be important risk indicators for long-term neurologic morbidity., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: The Chlamydia IgG antibody test (CAT) shows considerable variations in reported estimates of test accuracy, partly because of the use of different assays and cut-off values. The aim of this study was to reassess the accuracy of CAT in diagnosing tubal pathology by individual patient data (IPD) meta-analysis for three different CAT assays., Methods: We approached authors of primary studies that used micro-immunofluorescence tests (MIF), immunofluorescence tests (IF) or enzyme-linked immunosorbent assay tests (ELISA). Using the obtained IPD, we performed pooled receiver operator characteristics analysis and logistic regression analysis with a random effects model to compare the three assays. Tubal pathology was defined as either any tubal obstruction or bilateral tubal obstruction., Results: We acquired data of 14 primary studies containing data of 6191 women, of which data of 3453 women were available for analysis. The areas under the curve for ELISA, IF and MIF were 0.64, 0.65 and 0.75, respectively (P-value < 0.001) for any tubal pathology and 0.66, 0.66 and 0.77, respectively (P-value = 0.01) for bilateral tubal pathology., Conclusions: In Chlamydia antibody testing, MIF is superior in the assessment of tubal pathology. In the initial screen for tubal pathology MIF should therefore be the test of first choice.

Background: Conventional meta-analysis has estimated the sensitivity and specificity of hysterosalpingography (HSG) to be 65% and 83%. The impact of patient characteristics on the accuracy of HSG is unknown. The aim of this study was to assess by individual patient data meta-analysis whether the accuracy of HSG is associated with different patient characteristics., Methods: We approached authors of primary studies reporting on the accuracy of HSG using findings at laparoscopy as the reference. We assessed whether patient characteristics such as female age, duration of subfertility and a clinical history without risk factors for tubal pathology were associated with the accuracy of HSG, using a random intercept logistic regression model., Results: We acquired data of seven primary studies containing data of 4521 women. Pooled sensitivity and specificity of HSG were 53% and 87% for any tubal pathology and 46% and 95% for bilateral tubal pathology. In women without risk factors, the sensitivity of HSG was 38% for any tubal pathology, compared with 61% in women with risk factors (P = 0.005). For bilateral tubal pathology, these rates were 13% versus 47% (P = 0.01). For bilateral tubal pathology, the sensitivity of HSG decreased with age [factor 0.93 per year (P = 0.05)]. The specificity of HSG was very stable across all subgroups., Conclusions: The accuracy of HSG in detecting tubal pathology was similar in all subgroups, except for women without risk factors in whom sensitivity was lower, possibly due to false-positive results at laparoscopy. HSG is a useful tubal patency screening test for all infertile couples.

Objective: Although not formally supported by guidelines, random glucose testing (RGT) is frequently used to screen for gestational diabetes mellitus (GDM). Results on test accuracy are inconclusive. The aim of this study was to systematically review the literature and calculate summary estimates of accuracy measures of RGT as screening test for GDM., Study Design: Systematic review to identify studies comparing RGT to oral glucose tolerance testing before 32 weeks of pregnancy. A systematic search without language restrictions was performed in MEDLINE (1950 till April 2008) and EMBASE (1980 to April 2008). Study selection and data extraction were performed by two independent reviewers. Outcome measures were summary estimates of test accuracy of RGT., Results: Six studies were included, reporting on 3537 women. Due to the small number of studies and heterogeneity, no summary estimates of test accuracy were calculated. Reported sensitivities and specificities of individual studies varied. For 100% sensitivity, specificity was around 40%. For sensitivity of 60% specificity was at most 80%. When specificity approached 100%, sensitivity dropped to 20-30%., Conclusion: Available evidence on the accuracy of RGT to test for GDM is limited. Based on studies in our systematic review, we consider single random glucose measurement inadequate to screen for GDM., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Anti-Mullerian hormone (AMH) is a marker of ovarian reserve status and represents a good predictor of ovarian response to ovarian hyperstimulation. The aim of this study was to assess the accuracy of AMH and antral follicle count (AFC) as predictors of an excessive response in IVF/ICSI treatment., Methods: A systematic review and meta-analysis of the existing literature was performed. Studies were included if 2 × 2 tables for the outcome excessive response in IVF patients in relation to AMH/AFC could be constructed. Using a bivariate meta-analytic model, both summary point estimates for sensitivity and specificity were calculated, as well as summary ROC curves. Clinical value was analysed by calculating post-test probabilities of excessive response at optimal cut-off levels, as well as the corresponding abnormal test rates., Results: Nine studies reporting on AMH and five reporting on AFC were found. Summary estimates of sensitivity and specificity for AMH were 82 and 76%, respectively, and 82 and 80%, respectively, for AFC. Comparison of the summary estimates and ROC curves for AMH and AFC showed no statistical difference. Abnormal test rates for AMH and AFC amounted to ∼14 and 16%, respectively, at cut-off levels where test performance is optimal [likelihood ratio for a positive result (LR + ) > 8], with a post-test probability of ± 70%., Conclusions: Both AMH and AFC are accurate predictors of excessive response to ovarian hyperstimulation. Moreover, both tests appear to have clinical value. This opens ways to explore the potential of individualized FSH dose regimens based on ovarian reserve testing.

Objective: To investigate if ductus venosus (DV) pulsatility index for veins (PIV) and a-wave measurements can increase the accuracy of first-trimester Down syndrome screening in a high-risk population., Methods: The database of our fetal medicine unit was searched for all cases at increased first-trimester Down syndrome risk. Multivariable logistic regression was used to construct a prediction rule for chromosomal anomalies at any given maternal age, nuchal translucency multiples of the median (NT-MoM) and DV-PIV MoM. The discriminative ability of the model was assessed by using receiver-operating characteristics (ROC) analysis., Results: The study population included 445 fetuses. DV-PIV was increased (≥ 95(th) percentile) in 239 (54%) and DV a-wave was abnormal in 187 fetuses (42%). In this cohort, 80% of all chromosomal anomalies were identified by an increased DV-PIV and 68% by an abnormal a-wave. The odds of chromosomal anomalies increased by a factor of 4.2 per MoM increase in DV-PIV, adjusted for NT and maternal age. The area under the ROC curve for the prediction of chromosomal anomalies was 0.79. After correction for DV-PIV, DV a-wave did not significantly add to the prediction of chromosomal anomalies., Conclusion: In a population of fetuses at increased first-trimester risk for Down syndrome, the combination in a logistic regression model of NT, DV-PIV and maternal age can improve the accuracy of screening for trisomy 21 and other chromosomal anomalies. This is the first study that models the additional value of DV-PIV as a continuous variable to NT measurement alone in a high-risk first-trimester population., (Copyright © 2010 ISUOG. Published by John Wiley & Sons, Ltd.)

There is an ongoing debate whether tubal ectopic pregnancy should be treated by salpingotomy or salpingectomy. It is unknown which treatment women prefer in view of the potentially better fertility outcome but disadvantages of salpingotomy. This study investigated women surgically treated for tubal ectopic pregnancy and subfertile women desiring pregnancy and their preferences for salpingotomy relative to salpingectomy by means of a web-based discrete choice experiment consisting of 16 choice sets. Scenarios representing salpingotomy differed in three attributes: intrauterine pregnancy (IUP) chance, risk of persistent trophoblast and risk of repeat ectopic pregnancy. An 'opt out' alternative, representing salpingectomy, was similar for every choice set. A multinomial logistic regression model was used to analyse relative importance of the attributes. This study showed that the negative effect of repeat ectopic pregnancy was 1.6 times stronger on the preference of women compared with the positive effect of the spontaneous IUP rate. For all women, the risk of persistent trophoblast was acceptable if compensated by a small rise in the spontaneous IUP rate. The conclusion was that women preferred avoiding a repeat ectopic pregnancy to a higher probability of a spontaneous IUP in the surgical treatment of tubal ectopic pregnancy. An ectopic pregnancy occurs when a fertilized egg gets stuck inside the Fallopian tube where it starts growing instead of passing on to the uterus. This may lead to serious problems, such as internal bleeding and pain. Therefore, in the majority of women, it is necessary to remove the ectopic pregnancy by means of an operation. Two types of surgery are being used in removing the ectopic pregnancy. A conservative approach, salpingotomy, preserves the tube but bears the risk of incomplete removal of the pregnancy tissue (persistent trophoblast), which then needs additional treatment, and of a repeat ectopic pregnancy in the same tube in the future. A radical approach, salpingectomy, bears no risk of persistent trophoblast and limits the risk of repeat tubal pregnancy, but leaves only one tube for reproductive capacity. It is unknown which type of operation is better, especially for future fertility. We investigated women's preferences between these two treatments for ectopic pregnancy, i.e. does a better fertility prognosis outweigh the potential disadvantages of persistent trophoblast and an increased risk for ectopic pregnancy in the future? The study results show in the surgical treatment of tubal ectopic pregnancy that women preferred avoiding a repeat ectopic pregnancy to gaining a higher chance of a spontaneous intrauterine pregnancy. The risk of additional treatment in the case of persistent trophoblast after salpingotomy was acceptable if compensated by a small rise in intrauterine pregnancy rate., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Many perinatal interventions are performed to improve long-term neonatal outcome. To evaluate the long-term effect of a perinatal intervention follow-up of the child after discharge from the hospital is necessary because serious sequelae from perinatal complications frequently manifest themselves only after several years. However, long-term follow-up is time-consuming, is not in the awareness of obstetricians, is expensive and falls outside the funding-period of most obstetric studies. Consequently, short-term outcomes are often reported instead of the primary long-term end-point. With this project, we will assess the current state of affairs concerning follow-up after obstetric RCTs and we will develop multivariable prediction models for different long-term health outcomes. Furthermore, we would like to encourage other researchers participating in follow-up studies after large obstetric trials (> 350 women) to inform us about their studies so that we can include their follow-up study in our systematic review. We would invite these researchers also to join our effort and to collaborate with us on the external validation of our prediction models., Methods/design: A systematic review of neonatal follow-up after obstetric studies will be performed. All reviews of the Cochrane Pregnancy and Childbirth group will be assessed for reviews on interventions that aimed to improve neonatal outcome. Reviews on interventions primary looking at other aspects than neonatal outcome such as labour progress will also be included when these interventions can change the outcome of the neonate on the short or long-term. Our review will be limited to RCTs with more than 350 women. Information that will be extracted from these RCTs will address whether, how and for how long follow-up has been performed. However, in many cases long-term follow-up of the infants will not be feasible. An alternative solution to limited follow-up could be to develop prediction models to estimate long-term health outcomes of the newborn based on specific perinatal outcomes and other covariates. For the development of multivariable prediction models for several health outcomes, we will use data available from a Dutch cohort study of preterm (< 32 weeks) and/or small for gestational age infants (< 1500 g). These infants were born in The Netherlands in 1983 and followed until they reached the age of 19., Discussion: The systematic review will provide insight in the extent and methods used for follow-up assessments after obstetric RCTs in the past. The prediction models can be used by future studies to extrapolate short-term outcomes to a long-term horizon or to indicate for which neonates long-term follow-up is required, as their outcomes (either absence or presence of sequelae) cannot be adequately predicted from short-term outcomes and clinical background characteristics.

Background: Breech presentation occurs in 3 to 4% of all term pregnancies. External cephalic version (ECV) is proven effective to prevent vaginal breech deliveries and therefore it is recommended by clinical guidelines of the Royal Dutch Organisation for Midwives (KNOV) and the Dutch Society for Obstetrics and Gynaecology (NVOG). Implementation of ECV does not exceed 50 to 60% and probably less.We aim to improve the implementation of ECV to decrease maternal and neonatal morbidity and mortality due to breech presentations. This will be done by defining barriers and facilitators of implementation of ECV in the Netherlands. An innovative implementation strategy will be developed based on improved patient counselling and thorough instructions of health care providers for counselling., Method/design: The ultimate purpose of this implementation study is to improve counselling of pregnant women and information of clinicians to realize a better implementation of ECV.The first phase of the project is to detect the barriers and facilitators of ECV. The next step is to develop an implementation strategy to inform and counsel pregnant women with a breech presentation, and to inform and educate care providers. In the third phase, the effectiveness of the developed implementation strategy will be evaluated in a randomised trial. The study population is a random selection of midwives and gynaecologists from 60 to 100 hospitals and practices. Primary endpoints are number of counselled women. Secondary endpoints are process indicators, the amount of fetes in cephalic presentation at birth, complications due to ECV, the number of caesarean sections and perinatal condition of mother and child. Cost effectiveness of the implementation strategy will be measured., Discussion: This study will provide evidence for the cost effectiveness of a structural implementation of external cephalic versions to reduce the number of breech presentations at term., Trial Registration: Dutch Trial Register (NTR): 1878.

Background: Chest radiographs are often used to diagnose community-acquired pneumonia (CAP), to monitor response to treatment and to ensure complete resolution of pneumonia. However, radiological exams may not reflect the actual clinical condition of the patient., Objective: To compare the radiographic resolution of mild to moderately severe CAP to resolution of clinical symptoms as assessed by the physician or rated by the patient., Design: Prospective cohort study., Participants: One hundred nineteen patients admitted because of mild to moderately severe CAP with new pulmonary opacities., Main Measures: Radiographic resolution and clinical cure of CAP were determined at day 10 and 28. Radiographic resolution was defined as the absence of infection-related abnormalities; clinical cure was rated by the physician and defined by improvement of signs and symptoms. In addition, the CAP score, a patient-based symptom score, was calculated., Key Results: Radiographic resolution, clinical cure and normalization of the CAP score were observed in 30.8%, 93% and 32% of patients at day 10, and in 68.4%, 88.9% and 41.7% at day 28, respectively. More severe CAP (PSI score >90) was independently associated with delayed radiographic resolution at day 28 (OR 4.7, 95% CI 1.3-16.9). All 12 patients with deterioration of radiographic findings during follow-up had clinical evidence of treatment failure., Conclusions: In mild to moderately severe CAP, resolution of radiographic abnormalities and resolution of symptoms scored by the patient lag behind clinical cure assessed by physicians. Monitoring a favorable disease process by routine follow-up chest radiographs seems to have no additional value above following a patient's clinical course.

Decision making in healthcare often involves decision alternatives that vary on different dimensions in conflicting ways, such as health benefits and costs. In such cases, it is not always easy to identify the best option, as a trade-off has to be made. In preference studies, patients evaluate health states or healthcare strategies reflecting this trade-off. A focus that is restricted to only health outcomes in decision making may be too narrow. Patients also derive utility, or experience disutility, from healthcare processes themselves. A range of techniques is available for eliciting valuations of patients for these processes and other non-health outcomes. At present, it is unclear to what extent, and how, clinical evaluation studies have taken into account non-health outcomes. We performed a systematic review of trade-off and valuation studies to assess the extent to which valuations of process and non-health outcomes have actually been elicited from patients, in what specialty areas, and what techniques were used.We identified 567 articles that addressed patients' preferences involving non-health outcomes. The main therapeutic fields were oncology (17%), gynecology/obstetrics (11%), pulmonology (11%), cardiology (7%), gastroenterology (6%), and infectious diseases (6%). There was an absolute increase from the early 1980s (a handful of studies published each year) to recent years (almost 100 publications per year). We noticed a strong increase in elicitation techniques aimed at identification of determinants of patients' preferences.The number of studies addressing preferences for medical dilemmas involving non-health outcomes is steadily increasing and covers the whole spectrum of health-related interventions across all medical fields. A diversification in application fields as well as in research methods was observed, reflecting a lack of standardization. There is a need for methodological standards and evidence-based criteria to evaluate the methodological quality and clinical validity of studies that address preferences for dilemmas involving non-health outcomes.

Introduction: Results of the first randomized trial comparing on-demand versus planned-relaparotomy strategy in patients with severe peritonitis (RELAP trial) indicated no clear differences in primary outcomes. We now report the full economic evaluation for this trial, including detailed methods, nonmedical costs, further differentiated cost calculations, and robustness of different assumptions in sensitivity analyses., Methods: An economic evaluation was conducted from a societal perspective alongside a randomized controlled trial in 229 patients with severe secondary peritonitis and an acute physiology and chronic health evaluation (APACHE)-II score >or=11 from two academic and five regional teaching hospitals in the Netherlands. After the index laparotomy, patients were randomly allocated to an on-demand or a planned-relaparotomy strategy. Primary resource-utilization data were used to estimate mean total costs per patient during the index admission and after discharge until 1 year after the index operation. Overall differences in costs between the on-demand relaparotomy strategy and the planned strategy, as well as relative differences across several clinical subgroups, were evaluated., Results: Costs were substantially lower in the on-demand group (mean, 65,768 euro versus 83,450 euro per patient in the planned group; mean absolute difference, 17,682 euro; 95% CI, 5,062 euro to e29,004 euro). Relative differences in mean total costs per patient (approximately 21%) were robust to various alternative assumptions. Planned relaparotomy consistently generated more costs across the whole range of different courses of disease (quick recovery and few resources used on one end of the spectrum; slow recovery and many resources used on the other end). This difference in costs between the two surgical strategies also did not vary significantly across several clinical subgroups., Conclusions: The reduction in societal costs renders the on-demand strategy a more-efficient relaparotomy strategy in patients with severe peritonitis. These differences were found across the full range of healthcare resources as well as across patients with different courses of disease., Trial Registration: ISRCTN51729393.

Postmenopausal bleeding (PMB) is a common clinical problem. Patients with PMB have 10%-15% chance of having endometrial carcinoma and therefore the diagnostic workup is aimed at excluding malignancy. Patient characteristics can alter the probability of having endometrial carcinoma in patients with PMB; in certain groups of patients the incidence has been reported to be as high as 29%. Transvaginal sonography (TVS) is used as a first step in the diagnostic workup, but different authors have come to different conclusions assessing the accuracy of TVS for excluding endometrial carcinoma. Diagnostic procedures obtaining material for histological assessment (e.g., dilatation and curettage, hysteroscopy, and endometrial biopsy) can be more accurate but are also more invasive. The best diagnostic strategy for diagnosing endometrial carcinoma in patients with PMB still remains controversial. Future research should be focussed on achieving a higher accuracy of different diagnostic strategies.

Objective: We assessed the preferences of women with an adnexal mass for the mode of surgery., Methods: A structured interview was designed in which women, scheduled for surgery for an adnexal mass, were confronted with fictive scenarios of the different approaches. Women were asked at what probability of a false negative test result of frozen section diagnosis they would prefer frozen section diagnosis over primary radical surgery. Furthermore, the women were asked at what probability of ovarian malignancy they would prefer laparoscopy over laparotomy., Results: We interviewed 43 women. When the probability of frozen section diagnosis being false negative was set at 90%, 97% of the women preferred primary radical surgery. The mean threshold at which women switched their preference from primary radical surgery to frozen section diagnosis was at a risk of 49% on a false negative test result of frozen section diagnosis. In the choice between laparoscopy over laparotomy, the mean threshold at which the women switched their preference from laparoscopy to laparotomy was at a risk of 55% on ovarian malignancy., Conclusion: Women scheduled for surgery of an adnexal mass at low risk of ovarian malignancy, prefer frozen section diagnosis over primary radical surgery and prefer laparoscopy over laparotomy.

In the present study, women's preferences on advantages and disadvantages of laparoscopic hysterectomy (LH) and abdominal hysterectomy (AH) have been studied. Patients' preferences were evaluated in individual, structured interviews in women scheduled for hysterectomy and questionnaires in nurses. Forty-three patients and 39 nurses were included. After general information, 84% of patients and 74% of nurses preferred LH over AH. This preference did not change after supplying more detailed information or after hysterectomy. The avoidance of complications was indicated as the most important factor in the decision. More than half of the women evaluated a difference of 1% as the maximum acceptable risk of major complications. When confronted with scenarios based on current evidence, both patients and nurses prefer LH over AH. This study supports further implementation of LH in clinical practice. The actual major complication rate in hysterectomy, however, is perceived as high.

Aim: A prediction rule for gestational diabetes mellitus (GDM) could be helpful in early detection and increased efficiency of screening. A prediction rule by means of a clinical scoring system is available, but has never been validated externally. The aim of this study was to validate the scoring system., Methods: We used data from a prospective cohort study. Women were assigned a score based on age, BMI and ethnicity. Performance of the scoring system was evaluated in terms of discrimination and calibration (agreement between clinical score and observed probability of GDM). We compared the efficiency of a screening strategy derived from the scoring system with conventional screening., Results: We studied 1266 women. Forty-seven women had GDM (3.7%). The scoring system discriminated moderately (area under the curve=0.64 (95% CI 0.56-0.72)). Calibration was limited (chi(2)=8.89, p=0.06). The screening strategy derived from the scoring system reduced the number of women needed to be screened with 25% for a comparable detection rate to universal screening., Conclusion: Despite moderate discriminative capacity and calibration of the scoring system, the screening strategy based on the scoring system appears clinically useful. There is need for better prediction models for GDM.

Empirical data have challenged chronic posttraumatic stress disorder (PTSD) consisting of three dimensions. In the present study we aimed to determine the factor structure of acute posttraumatic symptoms in two recently traumatized samples. In sample 1, 203 civilian trauma survivors were administered the Davidson Trauma Scale (DTS) approximately 1 week posttrauma. In sample 2, 182 civilian treatment seeking trauma survivors completed the DTS at an average of 41.4 days posttrauma. Our confirmatory factor analyses indicated that a 4-factor intercorrelated model provided the best representation of the data in both samples. The four factors are best described as reexperiencing, active avoidance, dysphoria, and hyperarousal. For acute posttraumatic symptoms, the empirical data suggest to split the avoidance cluster into 'Active avoidance' and 'Dysphoria'-confirming findings in studies on chronic PTSD. In future revisions of the DSM, the diagnostic criteria for PTSD may need to be adapted to fit the research findings.

Objective: To assess the accuracy of the cervical smear in the diagnosis of endometrial cancer in women with postmenopausal bleeding, with an emphasis on the diagnostic relevance of normal endometrial cells., Study Design: Women presenting with abnormal postmenopausal bleeding, not using hormone replacement therapy, were included prospectively. Cervical cytology was coded according to both the Papanicolaou (Pap) classification and the Dutch coding system (CISOE-A), which classifies endometrial and other cell types separately. For both classification systems, likelihood ratios (LR) for the presence of (pre) malignancy of the endometrium were calculated., Results: We included 543 women with postmenopausal bleeding. A (pre) cancerous endometrial lesion was present in 64 women (11.7%). A Pap III increased the probability of (pre) malignancy (LR 3.5), whereas Pap IV and Pap V virtually proved the presence of carcinoma. The CISOE-A classification showed similar results. The presence of normal endometrial cells did not increase the probability of endometrial (pre) malignancy., Conclusion: Adding the results of the cervical smear to endometrial thickness could detect incidental endometrial cancers that are missed by transvaginal sonography (< 5 mm). In women with postmenopausal bleeding the presence of normal endometrial cells is not predictive of endometrial cancer.

Background: In clinical practice a diagnosis is based on a combination of clinical history, physical examination and additional diagnostic tests. At present, studies on diagnostic research often report the accuracy of tests without taking into account the information already known from history and examination. Due to this lack of information, together with variations in design and quality of studies, conventional meta-analyses based on these studies will not show the accuracy of the tests in real practice. By using individual patient data (IPD) to perform meta-analyses, the accuracy of tests can be assessed in relation to other patient characteristics and allows the development or evaluation of diagnostic algorithms for individual patients. In this study we will examine these potential benefits in four clinical diagnostic problems in the field of gynaecology, obstetrics and reproductive medicine., Methods/design: Based on earlier systematic reviews for each of the four clinical problems, studies are considered for inclusion. The first authors of the included studies will be invited to participate and share their original data. After assessment of validity and completeness the acquired datasets are merged. Based on these data, a series of analyses will be performed, including a systematic comparison of the results of the IPD meta-analysis with those of a conventional meta-analysis, development of multivariable models for clinical history alone and for the combination of history, physical examination and relevant diagnostic tests and development of clinical prediction rules for the individual patients. These will be made accessible for clinicians., Discussion: The use of IPD meta-analysis will allow evaluating accuracy of diagnostic tests in relation to other relevant information. Ultimately, this could increase the efficiency of the diagnostic work-up, e.g. by reducing the need for invasive tests and/or improving the accuracy of the diagnostic workup. This study will assess whether these benefits of IPD meta-analysis over conventional meta-analysis can be exploited and will provide a framework for future IPD meta-analyses in diagnostic and prognostic research.

Purpose: To determine the accuracy of endometrial thickness measurement with transvaginal ultrasonography (TVUS) to diagnose endometrial polyps in women with postmenopausal bleeding in whom a carcinoma has been ruled out., Methods: In women with postmenopausal bleeding, endometrial thickness was measured with TVUS. If endometrial thickness was >4 mm, office hysteroscopy was performed. At hysteroscopy, the uterine cavity was assessed for the presence of polyps. Patients with malignancy were excluded. We used receiver operating characteristics (ROC) analysis to assess the capacity of TVUS endometrial thickness measurement to diagnose endometrial polyps. Findings at hysteroscopy were considered to be the reference standard., Results: We included 178 patients with postmenopausal bleeding and endometrial thickness >4 mm. Hysteroscopy showed an endometrial polyp in 90 patients (50%). The ROC analysis revealed that endometrial thickness had an area under the curve of 0.64 in the diagnosis of endometrial polyps., Conclusion: In women with postmenopausal bleeding in whom carcinoma has been ruled out, measurement of endometrial thickness with TVUS is not useful in the diagnosis of endometrial polyps.

Objective: To determine the incidence and significance of recurrent postmenopausal bleeding among women diagnosed with an endometrial thickness < or =4 mm after a first episode of postmenopausal bleeding., Methods: Consecutive patients not using hormone replacement therapy (HRT) presenting with a first episode of postmenopausal bleeding and an endometrial thickness < or =4 mm at transvaginal ultrasonography (TVU) were managed expectantly. In case of recurrent bleeding, the patient was evaluated according to the hospital's local policy with TVU, office endometrial sampling, hysteroscopy or dilatation and curettage (D&C) or a combination of these tests. We evaluated the incidence of recurrent bleeding, potential risk factors for recurrent bleeding, and the diagnosis made after recurrent bleeding., Results: A total of 607 patients were registered with a first episode of postmenopausal bleeding, of whom 249 had an endometrial thickness < or =4 mm. Follow-up took place with a median of 174 weeks (range: 4-250 weeks). During follow-up, 25 of the 249 patients (10%; 95% CI: 6.6-14%) had recurrent bleeding. Median time until recurrence of bleeding was 49 weeks (range: 9-186 weeks). Two patients with recurrent bleeding turned out to have an endometrial carcinoma (8%; 95% CI: 2.2-25%), and 1 patient had a malignant melanoma. Time since menopause, age, body mass index, hypertension, diabetes and anticoagulants were not predictive for recurrent bleeding., Conclusion: The recurrence rate after a first episode of postmenopausal bleeding managed expectantly is low and cannot be predicted by patient characteristics. Patients with recurrent bleeding should be re-evaluated, as they bear a considerable risk of carcinoma.

Background: This study examined the accuracy of the 17-item Dutch version of the Davidson Trauma Scale (DTS) and the four-item SPAN (Startle, Physiological Arousal, Anger and Numbness) to detect survivors at risk for posttraumatic stress disorder (PTSD) within the first 2 weeks after the trauma., Methods: 203 civilian survivors of recent trauma with relatively mild symptoms completed the DTS a mean of 8.7 days after experiencing trauma. SPAN scores were computed from the DTS. At a mean of 64.6 days posttrauma, 160 respondents were assessed for diagnosis of PTSD with the Structured Interview for PTSD., Results: Receiver operating characteristic curves showed that the DTS showed good overall screening accuracy (84%). At a cut-off value of 64, the DTS demonstrated a sensitivity of 0.86, a specificity of 0.70, a positive predictive value (PPV) of 0.12, and a negative predictive value (NPV) of 0.98. Overall accuracy of the SPAN was good (89%). At a cut-off of 10 the SPAN showed a sensitivity of 0.86, a specificity of 0.86, a PPV of 0.22, and a NPV of 0.98. The low PPVs were possibly due to the low of prevalence of PTSD in our sample (4.4%)., Conclusions: This study shows that both the DTS and the SPAN are comparably accurate in screening early trauma survivors at risk for developing PTSD. The very brief four-item SPAN may be preferred over the longer 17-item DTS especially in settings in which time and resources are limited. Future studies should aim to cross-validate these results in random samples.

Objective: To estimate the incidence of recurrent postmenopausal bleeding among women who were diagnosed with an endometrial thickness greater than 4 mm., Methods: We designed a prospective cohort study and included consecutive women not using hormone replacement therapy, presenting with a first episode of postmenopausal bleeding. We evaluated patients who had an endometrial thickness greater than 4 mm at transvaginal ultrasonography and benign endometrial sampling; presence of carcinoma was ruled out by office endometrial sampling, hysteroscopy, and/or dilation and curettage. Time until recurrent bleeding was measured, and diagnosis at recurrent bleeding was recorded., Results: Among 318 patients who had an endometrial thickness greater than 4 mm, 222 patients had benign histology results and were available for follow-up. During follow-up, 47 (21%, 95% confidence interval 16-27%) patients had recurrent bleeding, with a median time to recurrent bleeding of 49 weeks (interquartile range 18 to 86 weeks). There was no difference with respect to recurrence rate between patients with polyp removal, patients with a normal hysteroscopy, and patients with office endometrial sampling alone at the initial workup. Two patients were diagnosed with atypical endometrial hyperplasia upon recurrent bleeding., Conclusion: The recurrence rate of postmenopausal bleeding in women with endometrial thickness greater than 4 mm is 20%. This recurrence rate is not related to incorporation of hysteroscopy or polyp removal at the initial workup., Level of Evidence: II.

Objectives: The optimal duration of antibiotic therapy in patients with uncomplicated pneumonia may be shorter than that recommended in the current guidelines. A shorter duration will probably also lead to a cost reduction. This study evaluates the costs associated with 3 versus 8 day antibiotic therapy and subsequent follow-up in patients hospitalized with mild-to-moderate-severe community-acquired pneumonia., Patients and Methods: The economic evaluation was based on primary resource utilization data collected within the framework of a randomized, double blind, placebo-controlled trial. As 3 day therapy was shown to be clinically not inferior to 8 day therapy, the cost-minimization analysis was performed based on direct medical and indirect non-medical costs, estimated from a societal perspective for the 28 days following hospital admission., Results: Lower costs of shorter therapy during hospital admission (euro 209 lower) were partially offset by higher costs for primary healthcare providers (euro 66 higher). The average costs generated per patient by resource utilization during admission and follow-up were estimated as euro 3,959 in the 3 day group versus euro 4,102 in the 8 day group (difference euro 143 in favour of shorter therapy). The difference was affected by changes in assumptions concerning the unit costs for hospital stay but was consistently in favour of shorter therapy., Conclusions: Shorter duration of antibiotic therapy in hospitalized patients with uncomplicated pneumonia does not result in a substantial substitution of resource utilization to primary healthcare providers. As 3 day antibiotic therapy does not lead to inferior clinical results, these findings support a 3 day therapy as a more efficient strategy.

Objective: To determine whether further histologic assessment can be omitted after office sampling produced a nondiagnostic specimen., Methods: Data were retrieved from a prospective cohort study of 913 women presenting with postmenopausal bleeding. This study was limited to women with an endometrial thickness either 5 mm or greater or that could not be measured, and in whom an endometrial biopsy performed in the office yielded nondiagnostic results., Results: Endometrial thickness was nonreassuring or unknown in 516 women, of whom 403 (78.1%) underwent office endometrial sampling. In 66 women the amount of tissue obtained was not sufficient for pathologic characterization. Further investigation revealed an endometrial malignancy in 3 of these 66 women and atypical hyperplasia in 1., Conclusion: In women with postmenopausal bleeding and a nonreassuring transvaginal ultrasound evaluation, a nondiagnostic office endometrial sample does not rule out endometrial cancer and further endometrial sampling is advisable.

Objective: To compare the accuracy measures of the random glucose test and the 50-g glucose challenge test as screening tests for gestational diabetes mellitus (GDM)., Research Design and Methods: In this prospective cohort study, pregnant women without preexisting diabetes in two perinatal centers in the Netherlands underwent a random glucose test and a 50-g glucose challenge test between 24 and 28 weeks of gestation. If one of the screening tests exceeded predefined threshold values, the 75-g oral glucose tolerance test (OGTT) was performed within 1 week. Furthermore, the OGTT was performed in a random sample of women in whom both screening tests were normal. GDM was considered present when the OGTT (reference test) exceeded predefined threshold values. Receiver operating characteristic (ROC) analysis was used to evaluate the performance of the two screening tests. The results were corrected for verification bias., Results: We included 1,301 women. The OGTT was performed in 322 women. After correction for verification bias, the random glucose test showed an area under the ROC curve of 0.69 (95% CI 0.61-0.78), whereas the glucose challenge test had an area under the curve of 0.88 (0.83-0.93). There was a significant difference in area under the curve of the two tests of 0.19 (0.11-0.27) in favor of the 50-g glucose challenge test., Conclusions: In screening for GDM, the 50-g glucose challenge test is more useful than the random glucose test.

Background: The aim of tubal testing is to identify women with bilateral tubal pathology in a timely manner, so they can be treated with IVF or tubal surgery. At present, it is unclear for which women early tubal testing is indicated, and in whom it can be deferred., Methods: Data on 3716 women who underwent tubal patency testing as a part of their routine fertility workup were used to relate elements in their medical history to the presence of tubal pathology. With multivariable logistic regression, we constructed two diagnostic models. One in which tubal disease was defined as occlusion and/or severe adhesions of at least one tube, whereas in a second model, tubal disease was defined as the presence of bilateral abnormalities., Results: Both models discriminated moderately well between women with and women without tubal disease with an area under the receiver-operating characteristic curve (AUC) of 0.65 (95% CI: 0.63-0.68) for any tubal pathology and 0.68 (95% CI: 0.65-0.71) for bilateral tubal pathology, respectively. However, the models could make an almost perfect distinction between women with a high and a low probability of tubal pathology. A decision rule in the form of a simple diagnostic score chart was developed for application of the models in clinical practice., Conclusions: In conclusion, the present study provides two easy to use decision rules that can accurately express a woman's probability of (severe) tubal pathology at the couple's first consultation. They could be used to select women for tubal testing more efficiently.

The objective is to assess among women with postmenopausal bleeding the relationship of age and time since menopause on one hand and the presence of endometrial cancer and atypical hyperplasia on the other hand. In a multicenter prospective cohort study, 614 women presenting with postmenopausal bleeding were included. Women underwent transvaginal sonography and, in cases where the endometrial thickness was >4 mm, endometrial sampling. Splines were used to assess the association between each of the continuous variables and (pre)malignancy of the endometrium. Subsequently, univariate and multivariate analysis were performed. The average age for women without (pre)malignancy was 61.7 years (SD 9.8). As malignant and premalignant cases were found to have similar age, these subgroups were merged in the analyses. Age was an independent predictor of (pre)malignancy. In women younger than 55 years, the odds ratio was 1.9 (95% CI: 1.1-3.3) for each year under 55 years of age and 1.03 (95% CI: 1.00-1.06) for each year over 55 years of age. The risk of (pre)malignancy of the endometrium was 4.9% in women less than 3 years postmenopausal versus 19.7% in women more than 20 years postmenopausal. However, in a multivariate analysis only age contributed to the prediction of risk. This study demonstrates that, in postmenopausal women with vaginal bleeding, the risk of (pre)malignancy of the endometrium is low in women under 50 years of age, increases considerably until 55 years of age, and rises only modestly with further advancing age. Future studies should explore whether these findings can be incorporated in the diagnostic work-up of women with postmenopausal bleeding.

Objective: To assess patients' preferences for diagnostic management of postmenopausal bleeding (PMB)., Design: A structured interview., Setting: A teaching hospital with office hysteroscopy facilities., Population: Thirty-nine women with PMB and with a completed work-up including an office hysteroscopy., Methods: A structured interview was taken from 39 women who had had an office hysteroscopy in the diagnostic work-up for PMB. Women were informed about the probability of endometrial carcinoma versus benign disease and about advantages and disadvantages of different diagnostic strategies, i.e. expectant management after ultrasound or complete diagnostic work-up, including invasive procedures., Main Outcome Measures: Women were informed about the probability of endometrial carcinoma versus benign disease and about advantages and disadvantages of different diagnostic strategies, i.e., expectant management after ultrasound or complete diagnostic work-up including invasive procedures. Women were asked to make a trade-off between different options., Results: Most women wanted to be 100% certain that carcinoma could be ruled out. Only 5% of the women were willing to accept more than 5% risk of false reassurance. If the risk of recurrent bleeding due to benign disease exceeded 25%, the majority of women would prefer immediate diagnosis and treatment of benign lesions., Conclusion: Women with PMB are prepared to undergo hysteroscopy to rule out any risk on cancer. This finding implicates that the measurement of endometrial thickness with transvaginal ultrasound as a first-line test in the assessment of PMB should be reconsidered.

Background: Preterm prelabour rupture of the membranes (PPROM) is an important clinical problem and a dilemma for the gynaecologist. On the one hand, awaiting spontaneous labour increases the probability of infectious disease for both mother and child, whereas on the other hand induction of labour leads to preterm birth with an increase in neonatal morbidity (e.g., respiratory distress syndrome (RDS)) and a possible rise in the number of instrumental deliveries., Methods/design: We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management. Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34+0 weeks until 37+0 weeks will be included in a multicentre prospective randomised controlled trial. We will compare early delivery with expectant monitoring. The primary outcome of this study is neonatal sepsis. Secondary outcome measures are maternal morbidity (chorioamnionitis, puerperal sepsis) and neonatal disease, instrumental delivery rate, maternal quality of life, maternal preferences and costs. We anticipate that a reduction of neonatal infection from 7.5% to 2.5% after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity. Under these assumptions, we aim to randomly allocate 520 women to two groups of 260 women each. Analysis will be by intention to treat. Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management. Long term outcomes will be evaluated using modelling., Discussion: This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis. CONTROLLED CLINICAL TRIAL REGISTER: ISRCTN29313500.

Background: To compare health related quality of life (HR-QoL) in patients surgically treated for secondary peritonitis to that of a healthy population. And to prospectively identify factors associated with poorer (lower) HR-QoL., Design: A prospective cohort of secondary peritonitis patients was mailed the EQ-5D and EQ-VAS 6-months following initial laparotomy., Setting: Multicenter study in two academic and seven regional teaching hospitals., Patients: 130 of the 155 eligible patients (84%) responded to the HR-QoL questionnaires., Results: HR-QoL was significantly worse on all dimensions in peritonitis patients than in a healthy reference population. Peritonitis characteristics at initial presentation were not associated with HR-QoL at six months. A more complicated course of the disease leading to longer hospitalization times and patients with an enterostomy had a negative impact on the mobility (p = 0.02), self-care (p < 0.001) and daily activities: (p = 0.01). In a multivariate analysis for the EQ-VAS every doubling of hospital stay decreases the EQ-VAS by 3.8 points (p = 0.015). Morbidity during the six-month follow-up was not found to be predictive for the EQ-5D or EQ-VAS., Conclusion: Six months following initial surgery, patients with secondary peritonitis report more problems in HR-QoL than a healthy reference population. Unfavorable disease characteristics at initial presentation were not predictive for poorer HR-QoL, but a more complicated course of the disease was most predictive of HR-QoL at 6 months.

Objective: The importance of validly identifying and incorporating patients' views for improving health care is generally acknowledged. Common approaches to assess patients' preferences are based on the quality adjusted life year (QALY) framework, but this ignores a number of aspects that may be relevant. As an alternative, we assessed patients' treatment preferences and trade-offs for five common systemic therapies for psoriasis., Study Design and Setting: Twenty-nine patients with moderate-to-severe psoriasis expressed treatment preferences for five oral and phototherapies and indicated the relative importance of various treatment attributes, such as adverse effects, discomforts, and safety measures. In a structured interview, they were presented with clinical scenarios that contained descriptions of process and outcome characteristics and illustrations of the anticipated treatment benefit., Results: Over all paired comparisons, methotrexate (33%), cyclosporin (30%), acitretin (15%), UV-B (14%), and PUVA (8%) were preferred to the other treatment. Patients were willing to trade-off their initial preference for more improvement of psoriasis., Conclusions: Psoriasis patients generally prefer oral to phototherapies and consider most adverse effects and several discomforts important for selecting treatment. Our scenario-based structured interview approach to treatment preferences allowed us to incorporate a broad spectrum of potentially relevant decision components in a clinically meaningful way.

Background: Medical history taking as well as Chlamydia antibody titre (CAT) testing are currently used in the selection of patients for diagnostic laparoscopy with tubal patency testing. Most research has focused on the predictive value of CAT in isolation from medical history. We assessed therefore whether the combination of medical history and CAT improves the efficiency of selecting patients for laparoscopy as compared to the use of either medical history or CAT., Methods: Data of 207 consecutive subfertile women were used to create multivariable logistic regression models for the prediction of tubal disease as diagnosed by diagnostic laparoscopy., Results: The model with data of medical history only had an area under the receiver operating characteristic curve (AUC) of 0.65 (95% CI 0.56-0.74). Addition of CAT increased the AUC to 0.70 (95% CI 0.62-0.78) (P = 0.065). CAT was positive in 40 women and showed a sensitivity of 0.37 (95% CI 0.26-0.49) for a specificity of 0.88 (95% CI 0.82-0.93). In CAT positive women, a blank medical history did not decrease the probability of tubal disease. Of the 167 women tested CAT negative, 23 (14%) still had a high probability of disease due to their medical history and 11 of them (48%) showed tubal abnormalities on diagnostic laparoscopy., Conclusions: CAT testing adds valuable information to a woman's risk profile based on her medical history. The combination of medical history taking and CAT testing has a better yield for diagnosing tubal disease than either of these alone.

Objectives: The aim of this study was to evaluate whether the efficiency of the current diagnostic work up following postmenopausal bleeding could be improved by diagnostic strategies that take into account characteristics of the women in addition to the currently recommended transvaginal measurement of endometrial thickness to determine for subsequent histological assessment., Design: Multicenter, prospective cohort study., Setting: A university hospital and seven teaching hospitals in the Netherlands., Sample: Consecutive women not using hormone replacement therapy, presenting with postmenopausal bleeding., Methods: Five hundred and forty women underwent transvaginal sonography, and in case of endometrial thickness (double layer) above 4 mm, subsequent endometrial sampling was performed. Presence of carcinoma was ruled out by the absence of abnormalities in histological specimen or by an uneventful follow up of at least 6 months., Main Outcome Measures: Probability of endometrial carcinoma was estimated by multivariable logistic regression models. For each diagnostic strategy, we calculated diagnostic accuracy (area under receiver operating characteristic curve [AUC]), negative predictive value (NPV) and the number of diagnostic procedures., Results: A strategy with transvaginal sonography alone with a fixed threshold incorrectly classified 0.7% of the women as nonmalignant (NPV: 99.3% [98.5-100%]), with 97% sensitivity and 56% specificity. A strategy integrating characteristics of the women with transvaginal sonography could result in less false reassurances (NPV: 99.6% [99.2-100%]), with only marginal decrease in diagnostic procedures, or a minor increase in false reassurances (NPV: 99.0% [98.3-100%]), with a substantial reduction (15-20%) in the procedures. AUCs associated with these strategies could improve from 0.76 (0.73-0.79) for transvaginal sonography alone to 0.90 (0.87-0.93) for the integrated strategy., Conclusion: Taking into account the characteristics of the women could increase the efficiency of the diagnostic work up for postmenopausal bleeding.

Study Objectives: The long-term outcomes of patients with community-acquired pneumonia (CAP) in terms of symptom resolution and health-related quality of life (HRQL) is unknown. Our objective was to determine the rate of symptom resolution using validated patient-based outcome measures, and to assess HRQL 18 months after the episode., Participants: Patients were recruited from a group enrolled in a randomized trial comparing two durations of treatment for CAP. Between 2000 and 2003, we included 102 adults with a mild-to-moderate-severe CAP (pneumonia severity index, < or = 110)., Interventions: CAP-related symptoms were assessed until month 18 using the CAP score. The CAP score was divided into respiratory and well-being sections to assess the recovery of respiratory and well-being symptoms separately. The HRQL was assessed at 18 months using the Medical Outcomes Study 36-item short form (SF-36) questionnaire and compared to a Dutch reference group., Results: Respiratory symptoms resolved within 14 days, while the well-being symptoms resolved more slowly. Taking the prepneumonia status into account, patients recovered fully from pneumonia after 6 months. Patients with comorbid conditions had significantly more symptoms prepneumonia and during follow-up than patients without comorbidities, but at all time points the proportion of patients that reached > or = 80% of the prepneumonia health level did not depend on comorbidity, age, or etiology. SF-36 scores at 18 months were significantly impaired in four of the eight dimensions for patients with comorbid illness, but did not differ from the reference population for patients without comorbid illness., Conclusion: Patients with mild-to-moderate-severe CAP recover fully from pneumonia after 6 months. The presence of symptoms beyond 28 days and any impairment in HRQL were found to reflect age and comorbidity rather than the persistent effects of the pneumonia itself.

Background: To assess the value of testing for ovarian reserve prior to a first cycle IVF incorporating patient and doctor valuation of mismatches between test results and treatment outcome., Methods: A decision model was developed for couples who were considering participation in an IVF programme. Three strategies were evaluated: (I) withholding IVF without prior testing, (II) testing for ovarian reserve, and then deciding on IVF treatment if ovarian reserve was estimated to be sufficient, and (III) treatment with IVF without prior ovarian reserve testing. The outcome considered was the birth of a child. The valuation of the combination of the strategy conducted and the outcome accomplished was expressed on a distress scale in units of 'IVF cycles that were performed in vain'. Correct treatment with IVF and correct withholding of IVF were considered to bring no distress. The distress of withholding IVF in case pregnancy occurred is consequently specified by the ratio of the expected distress after incorrect withholding IVF to the expected distress after incorrect performing IVF (distress ratio). We interviewed both patients and doctors to determine realistic estimates for this distress ratio., Results: The value of testing for ovarian reserve depends strongly on the expected pregnancy rate after IVF as well as on the valuation of the incorrect decisions from testing. For realistic ranges of the success rate after IVF and for distress ranges as were measured, treatment of all couples without testing was found to generate less distress than testing for ovarian reserve. The sensitivity and specificity of testing for ovarian reserve has to improve to 50 and 96% respectively, to make testing a valuable strategy., Conclusion: Based on the decision analysis, where current test accuracy and preference inventory among patients and physicians were used, testing for ovarian reserve seems not useful for current IVF programmes.

Background: The clinical benefits of glucose-insulin-potassium (GIK) and tight glycaemic control in patients undergoing coronary artery bypass grafting (CABG) may be partly explained by an anti-inflammatory effect. We applied GIK as a hyperinsulinaemic normoglycaemic clamp for >25 h and quantified its effect on systemic inflammation in patients undergoing CABG., Methods: Data obtained in 21 non-diabetic patients with normal left ventricular function scheduled for elective coronary artery surgery, who were randomly allocated to a control or GIK group, were analysed. In GIK patients, regular insulin was infused at a fixed rate of 0.1 IU kg(-1) h(-1). The infusion rate of glucose (30%) was adjusted to maintain blood glucose levels within a target range of 4.0-5.5 mmol litre(-1). Plasma concentrations of interleukins 6, 8 and 10, C-reactive protein (CRP) and serum amyloid A (SAA) were measured on the day of surgery and on the first and second postoperative days (POD1 and POD2)., Results: In the GIK group hypoglycaemia (glucose <2.2 mmol litre(-1)) did not occur, whereas hyperglycemia (glucose >6.1 mmol litre(-1)) developed in 15% of all measurements. In control patients, hyperglycaemia developed in >80% of all measurements in the presence of low endogenous insulin levels. CRP and SAA levels increased in both groups, with maximum levels measured on POD2. GIK treatment significantly reduced CRP and SAA levels. Interleukin levels increased significantly in both groups following cardiopulmonary bypass, but no differences were found between the groups., Conclusion: Hyperinsulinaemic normoglycaemic clamp is an effective method of maintaining tight glycaemic control in patients undergoing CABG and it attenuates the systemic inflammatory response in these patients. This effect may partly contribute to the reported beneficial effect of glycaemic control in patients undergoing CABG.

Background: A short but sensitive questionnaire evaluating changes in respiratory symptoms and well being during the treatment of community acquired pneumonia (CAP) is needed. We have developed a measurement and evaluated its psychometric properties in 67 patients admitted with CAP., Methods: The patients were asked to indicate the presence and severity of dyspnoea, coughing, coughing up sputum, coughing up sputum with ease, the colour of the sputum, fatigue, fitness, and their state of health. The item fatigue showed substantial overlap with fitness and was therefore excluded. The response of the patients to the remaining eight items was used to calculate a CAP score., Results: The percentage of missing data (0.2-1.7%), floor and ceiling effects (0.2/5.5%), internal consistency (Cronbach alpha = 0.87), and the intraclass correlation coefficient for test-retest reproducibility (0.83) met predefined criteria, indicating good acceptability and reliability. Face and clinical validity were satisfactory. Effect sizes under treatment were large, indicating high responsiveness., Conclusion: The newly developed CAP score is a simple, reliable, valid, and highly responsive instrument. This makes it scientifically sound and clinically relevant for measuring outcome when evaluating treatment strategies in CAP.

Objectives: To document and compare the costs of treatment of psoriasis with 2 established systemic agents that differ substantially in their unit costs: methotrexate vs cyclosporine., Design: Cost-minimization analysis within a randomized controlled trial., Setting: Outpatient dermatology department at an academic hospital., Patients: Adults with moderate to severe plaque psoriasis, with no previous methotrexate or cyclosporine treatment., Intervention: Sixteen weeks of treatment with methotrexate or cyclosporine and an additional 36 weeks of follow-up., Main Outcome Measures: Direct and indirect medical and nonmedical costs associated with resource utilization during treatment and follow-up., Results: Average cumulative total costs associated with 16 weeks of treatment were 1593 US dollars for methotrexate and 2114 US dollars for cyclosporine (521 US dollars less for methotrexate); during 36 weeks of follow-up, these costs were 2418 US dollars and 2306 US dollars, respectively. The overall difference in cumulative 1-year costs was 409 US dollars, or approximately 10% of the total costs., Conclusions: After 1 year, the overall difference in total costs between methotrexate and cyclosporine for 16 weeks of treatment and follow-up is relatively small. Systemic medication costs are only a fraction of the costs directly and indirectly generated by utilization of health care resources and associated with individual patients rather than with methotrexate or cyclosporine. Economic arguments can be supportive of but not decisive for individual patient decisions and guidelines for systemic therapy. Rational decision making for the treatment of psoriasis may include costs only within a long-term horizon and may consider the societal and patient benefits of different alternatives.

Background: Cyclosporin is an effective treatment for severe plaque psoriasis. Unfortunately, its use may be limited by time- and dose-related nephrotoxicity. Serum trough levels may be useful for monitoring the risk of nephrotoxicity., Objectives: To determine whether monitoring of trough levels is necessary in psoriasis patients undergoing short-term treatment with cyclosporin., Methods: A computerized and manual literature search identified studies on adults with plaque-type psoriasis treated with cyclosporin < or = 5 mg kg-1 daily, in which trough levels were measured in whole blood. Number of patients, treatment duration, formulation and dosage, renal function tests and trough levels were extracted. The association between renal function and trough levels was investigated. Additionally, in a randomized controlled trial on cyclosporin vs. methotrexate in moderate to severe psoriasis, cyclosporin trough levels were measured frequently in 20 patients during 12 weeks of treatment. The Pearson correlation coefficient between serum creatinine and cyclosporin trough levels was calculated., Results: Fifty-six articles were found concerning cyclosporin trough level measurements in psoriasis patients, of which eight were analysed. Many studies were excluded due to inappropriate cyclosporin dosages used. As data were heterogeneous and lacked various key parameters, a correlation study and a meta-analysis could not be performed. Instead, a quantitative description of the literature was given. No high mean trough levels or elevations of serum creatinine were described. In our clinical study, all the mean trough levels in 17 patients treated with cyclosporin 3 mg kg-1 daily were within the therapeutic range (< 200 ng mL-1). Elevated trough levels were found in two of three patients treated with cyclosporin 3-5 mg kg-1 daily. No signs of renal dysfunction were seen., Conclusions: The literature does not provide a definitive answer on whether monitoring cyclosporin trough levels in patients with psoriasis should be standard practice. Our own data show no need for cyclosporin trough level monitoring during short-term treatment with cyclosporin 3 mg kg-1 daily. However, when cyclosporin doses are > 3 mg kg-1 daily, monitoring may be indicated.

The reported findings of the European Consultation-Liaison Workgroup (ECLW) Collaborative Study describe consultation-liaison service delivery by 56 services from 11 European countries aggregated on a C-L service level. During the period of 1 year (1991), the participants applied a standardized, reliability tested method of patient data collection, and data were collected describing pertinent characteristics of the hospital, the C-L service, and the participating consultants. The consultation rate of 1% (median; 1.4% mean) underscores the discrepancy between epidemiology and the services delivered. The core function of C-L services in general hospitals is a quick, comprehensive emergency psychiatric function. Reasons to see patients were the following. deliberate self-harm (17%), substance abuse (7.2%), current psychiatric symptoms (38.6%), and unexplained physical complaints (18.6%) (all means). A significant number of patients are old and seriously ill. Mood disorders and organic mental disorders are most predominant (17.7%). Somatoform and dissociative disorders together constitute 7.5%. C-L services in European countries are mainly emergency psychiatric services and perform an important bridge function between primary, general health, and mental health care.

The authors developed a screening instrument to detect patients in need of complex care coordination at admission to a general hospital. On the basis of a series of risk factors for care complexity, the authors constructed a short, care complexity prediction instrument (COMPRI) and assessed its qualities. The COMPRI is an easily administered screening instrument that detects patients at risk for complex care needs for whom care coordination is indicated. COMPRI's predictive power exceeds all currently available case-mix instruments.