CCT: continuous care trial - a randomized controlled trial of the provision of continuous care during labor by maternity care assistants in the Netherlands.

BACKGROUND: In 2009, the Steering Committee for Pregnancy and Childbirth in the Netherlands recommended the implementation of continuous care during labor in order to improve perinatal outcomes. However, in current care, routine maternity caregivers are unable to provide this type of care, resulting in an implementation rate of less than 30%. Maternity care assistants (MCAs), who already play a nursing role in low risk births in the second stage of labor and in homecare during the postnatal period, might be able to fill this gap. In this study, we aim to explore the (cost) effectiveness of adding MCAs to routine first- and second-line maternity care, with the idea that these MCAs would offer continuous care to women during labor. METHODS: A randomized controlled trial (RCT) will be performed comparing continuous care (CC) with care-as-usual (CAU). All women intending to have a vaginal birth, who have an understanding of the Dutch language and are > 18 years of age, will be eligible for inclusion. The intervention consists of the provision of continuous care by a trained MCA from the moment the supervising maternity caregiver establishes that labor has started. The primary outcome will be use of epidural analgesia (EA). Our secondary outcomes will be referrals from primary care to secondary care, caesarean delivery, instrumental delivery, adverse outcomes associated with epidural (fever, augmentation of labor, prolonged labor, postpartum hemorrhage, duration of postpartum stay in hospital for mother and/or newborn), women's satisfaction with the birth experience, cost-effectiveness, and a budget impact analysis. Cost effectiveness will be calculated by QALY per prevented EA based on the utility index from the EQ-5D and the usage of healthcare services. A standardized sensitivity analysis will be carried out to quantify the outcome in addition to a budget impact analysis. In order to show a reduction from 25 to 17% in the primary outcome (alpha 0.05 and bèta 0.20), taking into account an extra 10% sample size for multi-level analysis and an attrition rate of 10%, 2 × 496 women will be needed (n = 992). DISCUSSION: We expect that adding MCAs to the routine maternity care team will result in a decrease in the use of epidural analgesia and subsequent costs without a reduction in patient satisfaction. It will therefore be a cost-effective intervention. TRIAL REGISTRATION: Trial Registration: Netherlands Trial Register, NL8065 . Registered 3 October 2019 - Retrospectively registered.

Prediction of incomplete primary debulking surgery in patients with advanced ovarian cancer: An external validation study of three models using computed tomography.

OBJECTIVE: To test the ability of three prospectively developed computed tomography (CT) models to predict incomplete primary debulking surgery in patients with advanced (International Federation of Gynecology and Obstetrics stages III-IV) ovarian cancer. METHODS: Three prediction models to predict incomplete surgery (any tumor residual >1cm in diameter) previously published by Ferrandina (models A and B) and by Gerestein were applied to a validation cohort consisting of 151 patients with advanced epithelial ovarian cancer. All patients were treated with primary debulking surgery in the Eastern part of the Netherlands between 2000 and 2009 and data were retrospectively collected. Three individual readers evaluated the radiographic parameters and gave a subjective assessment. Using the predicted probabilities from the models, the area under the curve (AUC) was calculated which represents the discriminative ability of the model. RESULTS: The AUC of the Ferrandina models was 0.56, 0.59 and 0.59 in model A, and 0.55, 0.60 and 0.59 in model B for readers 1, 2 and 3, respectively. The AUC of Gerestein's model was 0.69, 0.61 and 0.69 for readers 1, 2 and 3, respectively. AUC values of 0.69 and 0.63 for reader 1 and 3 were found for subjective assessment. CONCLUSIONS: Models to predict incomplete surgery in advanced ovarian cancer have limited predictive ability and their reproducibility is questionable. Subjective assessment seems as successful as applying predictive models. Present prediction models are not reliable enough to be used in clinical decision-making and should be interpreted with caution.

Surgery for Recurrent Epithelial Ovarian Cancer in the Netherlands: A Population-Based Cohort Study.

OBJECTIVE: The value of secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer is controversial. The aim of this population-based study was to investigate the role of SCS in the Netherlands. METHODS: Data of 408 patients who underwent SCS between 2000 and 2013 were retrospectively collected from 38 Dutch hospitals. Survival after complete and incomplete SCS was estimated by Kaplan-Meier curves. Factors associated with overall survival (OS) were explored with Cox regression. RESULTS: Median OS after SCS was 51 months (95% confidence interval [95% CI], 44.8-57.2). Complete SCS was achieved in 295 (72.3%) patients, with an OS of 57 months (95% CI, 49.0-65.0) compared with 28 months (95% CI, 20.8-35.2) in patients with incomplete SCS (log-rank test; P < 0.001). Nonserous histology (HR 0.65; 95% CI 0.45-0.95), a long progression free interval (hazard ratio [HR], 0.29; 95% CI, 0.07-1.18), a good performance status (HR, 0.68; 95% CI, 0.49-0.94), SCS without preoperative chemotherapy (HR, 0.72; 95% CI, 0.51-1.01), and complete SCS (HR, 0.46; 95% CI, 0.33-0.64) were prognostic factors for survival. CONCLUSIONS: This population-based retrospective study showed that there might be a role for SCS in recurrent epithelial ovarian cancer especially when complete SCS can be accomplished. However, before adopting SCS as a standard treatment modality for recurrent epithelial ovarian cancer, results of 3 ongoing prospectively randomized trials are needed.

Physicians' Awareness, Attitudes, and Experiences Regarding Imiquimod Treatment of Vaginal and Cervical Intraepithelial Neoplasia.

OBJECTIVE: The aim of the study was to assess awareness, attitudes, and current clinical experiences of gynecologists regarding imiquimod as a potential treatment modality for vaginal intraepithelial neoplasia (VAIN) and cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: A 37-item questionnaire consisting of both multiple choice and open questions was sent to all Dutch gynecologists who regularly perform colposcopies in all 87 Dutch hospitals, in December 2014. The outcomes were assessed using descriptive statistics. RESULTS: Gynecologists from 52 hospitals (60%) completed the questionnaire. Of the 77 respondents, 79% and 58% were aware of imiquimod for treating VAIN and CIN, respectively. Twelve and 5 respondents had used imiquimod to treat VAIN and CIN, respectively; most treatments were for intractable VAIN lesions and recurrent lesions and to avoid surgical treatment for CIN in patients with a future pregnancy wish. Most respondents reported successful treatment outcomes but frequent adverse effects. Most (96%) stated that they would consider using imiquimod to treat high-grade CIN in selected patients, but only upon additional evidence and inclusion into treatment guidelines. CONCLUSIONS: The awareness of imiquimod as a potential treatment for VAIN and CIN was limited, possibly because of the paucity of evidence regarding vaginal imiquimod efficacy, the lack of inclusion into guidelines, and the high frequency of adverse effects. Imiquimod was applied off-label in a limited number of selected patients, with good treatment results. The respondents generally had a positive attitude toward treating VAIN and CIN with imiquimod. Additional evidence on treatment efficacy and inclusion in treatment guidelines is necessary before application in clinical practice.

External validation of two prediction models of complete secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer.

OBJECTIVE: The purpose of this study was to validate the performance of two prediction models, the AGO score and the Tian model, of complete secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer. The predictive value of both models for survival controlled for the outcome of SCS was analyzed and known predictive factors for complete SCS were tested. METHODS: A population-based database with 408 patients, who underwent SCS between 2000 and 2013 in 38 Dutch hospitals, was used. The validation cohorts for the AGO score and the model of Tian contained 273 (66.9%) and 257 (63.0%) patients, respectively. RESULTS: The AGO score and Tian model showed a positive predictive value for complete SCS of 82.0% and 80.3% respectively, and a false negative rate of 68.5% and 55.6% respectively. A positive AGO score had no significant association with overall survival (HR 0.73; 95% CI 0.51-1.06) whereas the low risk score of the Tian model did (HR 0.62; 95% CI 0.41-0.93). A good performance status (OR 0.60; 95% CI 0.33-1.10) and the absence of ascites (OR 0.18; 95% CI 0.08-0.41) were prognostic factors for complete SCS. CONCLUSIONS: Both the AGO score and the model of Tian showed a high positive predictive value for complete SCS but also relatively high false negative rates. However, before the two prediction models can be applied in daily clinical practice the usefulness of SCS itself has to be proven first by the three ongoing randomized controlled trials: DESKTOP III trial, the GOG 213 trial and the Dutch SOCceR trial.

Cytoreductive surgery followed by chemotherapy versus chemotherapy alone for recurrent platinum-sensitive epithelial ovarian cancer (SOCceR trial): a multicenter randomised controlled study.

BACKGROUND: Improvement in treatment for patients with recurrent ovarian cancer is needed. Standard therapy in patients with platinum-sensitive recurrent ovarian cancer consists of platinum-based chemotherapy. Median overall survival is reported between 18 and 35 months. Currently, the role of surgery in recurrent ovarian cancer is not clear. In selective patients a survival benefit up to 62 months is reported for patients undergoing complete secondary cytoreductive surgery. Whether cytoreductive surgery in recurrent platinum-sensitive ovarian cancer is beneficial remains questionable due to the lack of level I-II evidence. METHODS/DESIGN: Multicentre randomized controlled trial, including all nine gynecologic oncologic centres in the Netherlands and their affiliated hospitals. Eligible patients are women, with first recurrence of FIGO stage Ic-IV platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer, who meet the inclusion criteria. Participants are randomized between the standard treatment consisting of at least six cycles of intravenous platinum based chemotherapy and the experimental treatment which consists of secondary cytoreductive surgery followed by at least six cycles of intravenous platinum based chemotherapy. Primary outcome measure is progression free survival. In total 230 patients will be randomized. Data will be analysed according to intention to treat. DISCUSSION: Where the role of cytoreductive surgery is widely accepted in the initial treatment of ovarian cancer, its value in recurrent platinum-sensitive epithelial ovarian cancer has not been established so far. A better understanding of the benefits and patients selection criteria for secondary cytoreductive surgery has to be obtained. Therefore the 4th ovarian cancer consensus conference in 2010 stated that randomized controlled phase 3 trials evaluating the role of surgery in platinum-sensitive recurrent epithelial ovarian cancer are urgently needed. We present a recently started multicentre randomized controlled trial that will investigate the role of secondary cytoreductive surgery followed by chemotherapy will improve progression free survival in selected patients with first recurrence of platinum-sensitive epithelial ovarian cancer.

The role of surgery in the management of patients with platinum-sensitive recurrent ovarian cancer: survey among Dutch gynecologists and medical oncologists.

OBJECTIVE: Evidence of randomized comparative clinical trials on surgery in recurrent platinum-sensitive ovarian cancer is non-existing. Three randomized phase 3 trials are ongoing. The aim of this study is to evaluate the current opinion of Dutch gynecologists and medical oncologists awaiting the results of these three trials. METHODS: A 16-item questionnaire was sent to all gynecologists (N=124) and medical oncologists (N=195) with special interest in gynecologic oncology in the Netherlands. The data were collected and analyzed using descriptive statistics. RESULTS: In total, 80 (65.0%) gynecologists and 67 (34.0%) medical oncologists responded. Among the respondents, 11.3% and 26.9% were not convinced of the benefit of secondary cytoreductive surgery, respectively. For most gynecologists and medical oncologists completeness of primary surgery (74.6% and 75.5%, respectively) and performance status (100% and 98%, respectively) were important factors when considering surgery. For only about 17.5% of all respondents diagnostic laparoscopy before surgery is a prerequisite. Most respondents (81.7% and 87.8%, respectively) would use platinum-based chemotherapy with paclitaxel as their agents of choice after surgery. In general medical oncologists settle for a smaller gain in both progression free as well as overall survival than gynecologists. CONCLUSIONS: Although most gynecologists and medical oncologists are already convinced of the usefulness of secondary cytoreductive surgery in certain patients, a better understanding of the real advantages and disadvantages and patient's selection criteria for secondary cytoreductive surgery will be achieved after the completion of three ongoing randomized controlled trials (DESKTOP III, GOG 213 and the SOCceR).

The effects of COVID-19 restrictions and other perinatal factors on women's sense of control during childbirth: a prospective cohort study.

BACKGROUND: Restrictions around childbirth, introduced during the COVID-19 pandemic in 2020, could decrease maternal feelings of control during birth. The aim of this study was to compare the sense of control of women who gave birth during the COVID-19 pandemic with women who gave birth before COVID-19. The secondary objective was to identify other factors independently associated with women's sense of control during birth. METHODS: A prospective cohort study, in a sub-cohort of 504 women from a larger cohort (Continuous Care Trial (CCT), n = 992), was conducted. Sense of control was measured by the Labor Agentry Scale (LAS). Perinatal factors independently associated with women's sense of control during birth were identified using multiple linear regression. RESULTS: Giving birth during the COVID-19 pandemic did not influence women's sense of control during birth. Factors statistically significantly related to women's sense of control were Dutch ethnic background (ß 4.787, 95%-CI 1.319 to 8.254), antenatal worry (ß - 4.049, 95%-CI -7.516 to -.581), antenatal anxiety (ß - 4.677, 95%-CI -7.751 to 1.603) and analgesics during birth (ß - 3.672, 95%-CI -6.269 to -1.075). CONCLUSIONS: Despite the introduction of restrictions, birth during the COVID-19 pandemic was not associated with a decrease of women's sense of control.

STop OVarian CAncer (STOPOVCA) young: Protocol for a multicenter follow-up study to determine the long-term effects of opportunistic salpingectomy on age at menopause.

BACKGROUND: Opportunistic salpingectomy comprises additional bilateral salpingectomy during abdominal surgery as a prophylactic method to reduce the risk of ovarian cancer. However, opportunistic salpingectomy may potentially damage (micro)blood circulation to the ovaries, resulting in earlier onset of menopause. PRIMARY OBJECTIVE: To evaluate the long-term effects of opportunistic salpingectomy on the onset of menopause in women who underwent sterilization through salpingectomy compared with a control group who underwent sterilization by tubal ligation or no surgery at all. STUDY HYPOTHESIS: Opportunistic salpingectomy does not lower the mean age at onset of menopause. TRIAL DESIGN: In a multicenter observational noninferiority study, we will prospectively compare the age at menopause of women initially aged 35-45 who underwent sterilization through opportunistic salpingectomy with a similarly aged control group who underwent sterilization by tubal ligation or no sterilization. Participants will be asked to complete an annual questionnaire on onset of menopause to eventually determine whether there is more than a one-year decrease in mean age at onset of menopause in the opportunistic salpingectomy group. Follow-up will last until determination of menopause, with a maximum of 15 years. MAJOR INCLUSION/EXCLUSION CRITERIA: Inclusion criteria: pre-menopausal; age between 35 and 45; intact ovaries. EXCLUSION CRITERIA: post-menopausal; previous bilateral salpingectomy or oophorectomy; previous hysterectomy; abnormal karyotype; previous or current chemotherapy or pelvic radiation. PRIMARY ENDPOINT(S): Determination of age of menopause measured by annual questionnaire. SAMPLE SIZE: 1200 (400 intervention group; 800 control group). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: It is estimated that recruitment will be completed by 2023 and results will be published by 2039. GOV IDENTIFIER: NCT04757922 PROTOCOL VERSION: : Version 1, February 2021.

[Unexplained cyanosis in two newborns: neonatal methemoglobinemia after maternal perineal infiltration of prilocaine]. / Onbegrepen cyanose bij twee neonaten.

BACKGROUND: Methemoglobinemia is a rare cause of neonatal cyanosis in the newborn. It is considered a medical emergency. Failure of recognition or appropriated treatment could result in serious disease and neonatal death. Neonatal methemoglobinemia can be caused by both hereditary and acquired factors. CASE DESCRIPTION: We present two cases of newborns who developed severe cyanosis a few hours after birth due to methemoglobinemia. This was thought to be related to the local maternal perineal infiltration of prilocaine during childbirth. Though rare, prilocaine is the most potent agent to induce methemoglobinemia compared to other local aneasthetics. After intravenous administration of methylene blue, both newborns fully recovered. CONCLUSION: Neonatal methemoglobinemia is a rare and potentially fatal complication of local anesthetics, particularly prilocaine, administered to the mother during childbirth. Midwives, obstetricians, gynecologists and pediatricians should be aware of this complication. The use of other local anesthetics, including lidocaine, should be considered.

Mifepristone followed by misoprostol compared with placebo followed by misoprostol as medical treatment for early pregnancy loss (the Triple M trial): A double-blind placebo-controlled randomised trial.

BACKGROUND: Worldwide, millions of women seek treatment for early pregnancy loss (EPL) annually. Medical management with misoprostol is widely used, but only effective 60% of the time. Pre-treatment with mifepristone prior to misoprostol might improve the success rate of medical management. METHODS: This was a multi-centre, double-blind, placebo-controlled randomised trial in 17 Dutch hospitals. Women with a non-viable pregnancy between 6 and 14 weeks of gestation were eligible for inclusion after at least one week of expectant management. Participants were randomised (1:1) between oral mifepristone 600 mg or an oral placebo tablet. Participants took 400 µg misoprostol orally, repeated after four hours on day two and, if necessary, day three. Primary outcome was expulsion of gestational sac and endometrial thickness <15 mm after 6-8 weeks. Analyses were done according to intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT03212352. FINDINGS: Between June 28th 2018 and January 8th 2020, 175 women were randomised to mifepristone and 176 to placebo, including 344 in the intention-to-treat analysis. In the mifepristone group 136 (79•1%) of 172 participants reached complete evacuation compared to 101 (58•7%) of 172 participants in the placebo group (p<0•0001, RR 1•35, 95% CI 1•16-1•56). Incidence of serious adverse events was significantly lower in the mifepristone group with 24 (14%) patients affected versus 55 (32%) in the placebo group (p = 0•0005) (Table 3). INTERPRETATION: Pre-treatment with mifepristone prior to misoprostol was more effective than misoprostol alone in managing EPL. FUNDING: Healthcare Insurers Innovation Foundation, Radboud University Medical Centre, Canisius Wilhelmina Hospital.

Perioperative changes in serum CA125 levels: a prognostic factor for disease-specific survival in patients with ovarian cancer.

OBJECTIVE: In patients with advanced stage epithelial ovarian cancer (EOC) the volume of residual tumor after debulking is known as prognostic factor for survival. We wanted to examine the relationship between postoperative decline in serum CA125 and residual disease after cytoreductive surgery and evaluate perioperative changes in serum CA125 levels as predictor for disease-specific survival. METHODS: A retrospective study was conducted of patients with FIGO stage IIb-IV EOC treated with cytoreductive surgery, followed by chemotherapy between 1996 and 2010 in three hospitals in the Southeastern region of the Netherlands. Data were analyzed with the use of multilevel linear regression and Cox-proportional hazard regression models. RESULTS: A postoperative decline in serum CA125 level of ≥80% was associated with complete primary cytoreduction (p=0.035). Univariate analyses showed favorable associations with survival for both the degree of decline in serum CA125 and residual tumor after primary cytoreduction. In multivariate analyses the decline in serum CA125 but not the outcome of surgery remained significantly associated with better survival (HR(50%-79%)=0.52 [95% CI: 0.28-0.96] and HR(≥80%)=0.26 [95% CI: 0.13-0.54] vs. the serum CA125 decline of <50% [p<0.001]). CONCLUSION: The current study, although hampered by possible biases, suggests that the perioperative decline in serum CA125 is an early biomarker that predicts disease-specific survival in patients who underwent primary cytoreductive surgery for advanced stage EOC. If confirmed prospectively, the perioperative change in serum CA125 could be a better marker for residual tumor volume after primary cytoreductive surgery (and therewith disease-specific survival) than the surgeons' estimation of residual tumor volume.

Accuracy of C-reactive protein determination in predicting chorioamnionitis and neonatal infection in pregnant women with premature rupture of membranes: a systematic review.

Preterm premature rupture of the fetal membranes (PPROM) is associated with intra-uterine infection. Early detection of intra-uterine infection may help prevent neonatal sepsis. C-reactive protein (CRP) is an acute phase protein often elevated when inflammation is present. The aim of this review was to assess whether CRP accurately predicts chorioamnionitis and/or neonatal sepsis in women with PPROM. We searched Medline and Embase databases for articles reporting on CRP and chorioamnionitis and/or neonatal sepsis. Two reviewers extracted clinical and methodological study characteristics and test accuracy data. Accurate data were used to form 2 x 2 data tables comparing CRP and the occurrence of infection. For the selected studies, sensitivity and specificity of CRP in the prediction of histological chorioamnionitis, clinical chorioamnionitis and neonatal sepsis were calculated separately. A bivariate meta-regression model was used to calculate pooled estimates of sensitivity and specificity. The search revealed 200 articles, of which only five met the inclusion criteria. These five articles reported on 381 patients, of which four articles (227 patients) reported on CRP as a predictor for histological chorioamnionitis and four studies (330 patients) reported on CRP as a predictor for clinical chorioamnionitis. None of the selected articles fulfilled our criteria for the use of CRP as a predictor of neonatal sepsis. CRP was moderately predictive of histological chorioamnionitis. Unfortunately, the studies of clinical chorioamnionitis were too heterogeneous to pool data. Current literature does not support the use of CRP in women with PPROM.