Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial.

Importance: Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown.

Objective: To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants.

Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial): A multicenter randomized controlled trial.

Background: Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia.

Effect of Pessary vs Surgery on Patient-Reported Improvement in Patients With Symptomatic Pelvic Organ Prolapse: A Randomized Clinical Trial.

Importance: Pelvic organ prolapse is a prevalent condition among women that negatively affects their quality of life. With increasing life expectancy, the global need for cost-effective care for women with pelvic organ prolapse will continue to increase.

Objective: To investigate whether treatment with a pessary is noninferior to surgery among patients with symptomatic pelvic organ prolapse.

Working conditions in women with multiple pregnancy-the impact on preterm birth and adherence to guidelines: a prospective cohort study.

Background: Women with multiple pregnancies are at risk for maternal complications such as preterm birth. Hazardous working conditions, such as physically demanding work and long and irregular working hours, might increase the risk of preterm birth.

Objective: This study primarily aimed to determine whether certain working conditions up to 20 weeks of pregnancy increase the risk of preterm birth in multiple pregnancies.

Elective induction of labour and expectant management in late-term pregnancy: A prospective cohort study alongside the INDEX randomised controlled trial.

Objective: To assess adverse perinatal outcomes and caesarean section of low-risk women receiving elective induction of labour at 41 weeks or expectant management until 42 weeks according to their preferred and actual management strategy.

Design: Multicentre prospective cohort study alongside RCT.

Setting: 90 midwifery practices and 12 hospitals in the Netherlands.

Endometrial ablation plus levonorgestrel releasing intrauterine system versus endometrial ablation alone in women with heavy menstrual bleeding: study protocol of a multicentre randomised controlled trial; MIRA2 trial.

Background: It is estimated that between 12 to 25% of women who undergo an endometrial ablation for heavy menstrual bleeding (HMB) are dissatisfied after two years because of recurrent menstrual bleeding and/or cyclical pelvic pain, with around 15% of these women ultimately having a hysterectomy. The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) immediately after endometrial ablation may inactivate residual untreated endometrium and/or inhibit the regeneration of endometrial tissue. Furthermore, the LNG-IUS may prevent agglutination of the uterine walls preventing intrauterine adhesion formation associated with endometrial ablation.

Working conditions in low risk nulliparous women in The Netherlands: are legislation and guidelines a guarantee for a healthy working environment? A cohort study.

Objective: Hazardous working conditions increase the risk of adverse pregnancy outcomes. In this study, we examine adherence to legislation and guidelines aimed at improving working conditions in pregnancy.

Methods: Between 2014 and 2016, we recruited a prospective cohort of low-risk nulliparous pregnant women in paid employment or self-employed in 16 community midwifery practices in The Netherlands.

Marketing Authorization Applications Made to the European Medicines Agency in 2018-2019: What was the Contribution of Real-World Evidence?

Information derived from routinely collected real-world data has for a long time been used to support regulatory decision making on the safety of drugs and has more recently been used to support marketing authorization submissions to regulators. There is a lack of detailed information on the use and types of this real-world evidence (RWE) as submitted to regulators. We used resources held by the European Medicines Agency (EMA) to describe the characteristics of RWE included in new marketing authorization applications (MAAs) and extensions of indication (EOIs) for already authorized products submitted to the EMA in 2018 and 2019.

The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study.

Background: Routine assessment in (near) term pregnancy is often inaccurate for the identification of fetuses who are mild to moderately compromised due to placental insufficiency and are at risk of adverse outcomes, especially when fetal size is seemingly within normal range for gestational age. Although biometric measurements and cardiotocography are frequently used, it is known that these techniques have low sensitivity and specificity. In clinical practice this diagnostic uncertainty results in considerable 'over treatment' of women with healthy fetuses whilst truly compromised fetuses remain unidentified.

Predictive factors for failure of the levonorgestrel releasing intrauterine system in women with heavy menstrual bleeding.

Background: This study was conducted to identify factors that are associated with failure of treatment using the levonorgestrel releasing intrauterine system (LNG-IUS) in women with heavy menstrual bleeding.

Methods: For this study, data of a cohort of women treated with an LNG-IUS was used. Women who suffered from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future child wish, were recruited in hospitals and general practices in the Netherlands.

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial.

Introduction: There is little evidence to guide the timing of delivery of women with early-onset severe preeclampsia. We hypothesize that immediate delivery is not inferior for neonatal outcome but reduces maternal complications compared with temporizing management.

Material And Methods: This Dutch multicenter open-label randomized clinical trial investigated non-inferiority for neonatal outcome of temporizing management as compared with immediate delivery (TOTEM NTR 2986) in women between 27 and 33 weeks of gestation admitted for early-onset severe preeclampsia with or without HELLP syndrome.

Treatment of women with heavy menstrual bleeding: Results of a prospective cohort study alongside a randomised controlled trial.

Objective: The objective of this study was to compare the reintervention rate of women who opted for treatment with the levonorgestrel-releasing intrauterine system (LNG-IUS) to women who opted for endometrial ablation. Furthermore, the difference in reintervention rate between women in this observational cohort and women who were randomised was compared, with the hypothesis that women who actively decide on treatment have lower reintervention rates compared to women in a RCT.

Study Design: An observational cohort study alongside a multicentre randomised controlled trial (RCT) was conducted between April 2012 and January 2016, with a follow-up time of 24 months, in 26 hospitals and nearby general practices in the Netherlands.

Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials.

Background: The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding.

Background: Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding.

Objective: This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding.

Induction of labour at 41 weeks versus expectant management until 42 weeks (INDEX): multicentre, randomised non-inferiority trial.

Objective: To compare induction of labour at 41 weeks with expectant management until 42 weeks in low risk women.

Design: Open label, randomised controlled non-inferiority trial.

Setting: 123 primary care midwifery practices and 45 hospitals (secondary care) in the Netherlands, 2012-16.

Long-term use of 5α-reductase inhibitors and the risk of male breast cancer.

Background: The 5α-reductase inhibitors (5-ARI) finasteride and dutasteride are indicated for the treatment of lower urinary tract symptoms caused by benign prostatic hyperplasia. Case reports have suggested that 5-ARIs increase the risk for male breast cancer, with no conclusive evidence. The objective of this study was to quantify the association between use of 5-ARIs and the risk for male breast cancer.

Concurrent use of statins and hormone therapy and risk of venous thromboembolism in postmenopausal women: a population-based case-control study.

Objective: Statins and hormone therapy (HT), often used concurrently in postmenopausal women, have antagonist effects on the risk of venous thromboembolism (VTE). This study aims to determine whether statins attenuate the increased VTE risk associated with HT.

Methods: We conducted a nested case-control study within a population-based cohort of women aged 50 to 79 years between January 1, 1987 and March 1, 2008, who were identified from the UK General Practice Research Database.

Post-approval safety issues with innovative drugs: a European cohort study.

Background: At time of approval, knowledge of the full benefit risk of any drug is limited, in particular with regards to safety. Post-approval surveillance of potential drug safety concerns is recognized as an important task of regulatory agencies. For innovative, often first-in-class drugs, safety knowledge at time of approval is often even less extensive and these may require tighter scrutiny post approval.

Number of patients studied prior to approval of new medicines: a database analysis.

Background: At the time of approval of a new medicine, there are few long-term data on the medicine's benefit-risk balance. Clinical trials are designed to demonstrate efficacy, but have major limitations with regard to safety in terms of patient exposure and length of follow-up. This study of the number of patients who had been administered medicines at the time of medicine approval by the European Medicines Agency aimed to determine the total number of patients studied, as well as the number of patients studied long term for chronic medication use, compared with the International Conference on Harmonisation's E1 guideline recommendations.

Potential misinterpretation of treatment effects due to use of odds ratios and logistic regression in randomized controlled trials.

Background: In randomized controlled trials (RCTs), the odds ratio (OR) can substantially overestimate the risk ratio (RR) if the incidence of the outcome is over 10%. This study determined the frequency of use of ORs, the frequency of overestimation of the OR as compared with its accompanying RR in published RCTs, and we assessed how often regression models that calculate RRs were used.

Methods: We included 288 RCTs published in 2008 in five major general medical journals (Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, New England Journal of Medicine).