Does the risk of hypersensitivity reactions to iopromide differ by sex, race, or across regions/countries? An analysis of 152 233 patients from 4 observational studies and the company's pharmacovigilance database.

Objective: To analyse the potential impact of patients' sex, race, and region/country on the risk of hypersensitivity reactions after intra-venous or intra-arterial administration of iopromide.

Methods: Two analyses were performed. (1) The "Phase-IV-Analysis" evaluated an integrated pooled database of 4 non-interventional studies.

Sharing Medical Big Data While Preserving Patient Confidentiality in Innovative Medicines Initiative: A Summary and Case Report from BigData@Heart.

Sharing individual patient data (IPD) is a simple concept but complex to achieve due to data privacy and data security concerns, underdeveloped guidelines, and legal barriers. Sharing IPD is additionally difficult in big data-driven collaborations such as Bigdata@Heart in the Innovative Medicines Initiative, due to competing interests between diverse consortium members. One project within BigData@Heart, case study 1, needed to pool data from seven heterogeneous data sets: five randomized controlled trials from three different industry partners, and two disease registries.

Accuracy of Breast Ultrasonography and Mammography in Comparison with Postoperative Histopathology in Breast Cancer Patients after Neoadjuvant Chemotherapy.

Introduction: Nowadays chemotherapy in breast cancer patients is optionally applied neoadjuvant, which allows for testing of tumor response to the chemotherapeutical treatment in vivo, as well as allowing a greater number of patients to benefit from a subsequent breast-conserving surgery.

Material And Methods: We compared breast ultrasonography, mammography, and clinical examination (palpation) results with postoperative histopathological findings after neoadjuvant chemotherapy, aiming to determine the most accurate prediction of complete remission and tumor-free resection margins. To this end, clinical and imaging data of 184 patients (193 tumors) with confirmed diagnosis of breast cancer and neoadjuvant therapy were analyzed.

Substituting a randomised placebo control group with a historical placebo control in an endometriosis pain trial: a case study re-evaluating trial data using historical control data from another trial.

Objective: The substitution of an in-study control population with a historical control (HC) population is considered a viable option for reducing the necessary recruitment of control patients. However, it is necessary to evaluate whether this method is applicable to studies on indications targeting endometriosis-associated pelvic pain (EAPP). This study aims to evaluate the potential bias in the results of an EAPP study with an HC arm.

Sex differences in the generalizability of randomized clinical trials in heart failure with reduced ejection fraction.

Aims: In order to understand how sex differences impact the generalizability of randomized clinical trials (RCTs) in patients with heart failure (HF) and reduced ejection fraction (HFrEF), we sought to compare clinical characteristics and clinical outcomes between RCTs and HF observational registries stratified by sex.

Methods And Results: Data from two HF registries and five HFrEF RCTs were used to create three subpopulations: one RCT population (n = 16 917; 21.7% females), registry patients eligible for RCT inclusion (n = 26 104; 31.

Postpartum Assessment of the Correlation between Serum Hormone Levels of Estradiol, Progesterone, Prolactin and ß-HCG and Blood Pressure Measurements in Pre-Eclampsia Patients.

Preeclampsia is a pregnancy-related hypertensive disease. Aberrant hormone levels have been implicated in blood pressure disorders. This study investigated the association of postpartum maternal serum hormone levels of estradiol, progesterone, prolactin, and ß-HCG with poorer PE-related complications including arterial hypertension.

Risk of Hypersensitivity Reactions to Iopromide in Children and Elderly: An Analysis of 132,850 Patients From 4 Observational Studies and Pharmacovigilance Covering >288 Million Administrations.

Purpose: The aim of this study was to analyze the risk of hypersensitivity reactions (HSRs) to iopromide in children and elderly patients in comparison to adults.

Materials And Methods: Four observational studies were pooled and analyzed (analysis I). In addition, spontaneous reports from 1985 to 2020 from the pharmacovigilance database were evaluated (analysis II).

Comparison of Maternal Serum Levels and Placental mRNA Levels of Dickkopf-1 in Preeclamptic and Normal Pregnant Women at Delivery.

Preeclampsia remains a major cause of perinatal and maternal mortality and morbidity worldwide. Wnt/β-catenin signaling is known to be critically involved in placenta development processes. Dickkopf-1 (DKK1) is a key regulator of this transduction pathway.

Real world data on symptomology and diagnostic approaches of 27,840 women living with endometriosis.

Endometriosis is a chronic disease that requires a suitable, lifelong treatment. To our knowledge, the Visanne Post-approval Observational Study (VIPOS) is to date the largest real-world, non-interventional study investigating hormonal management of endometriosis. We describe women's experiences of endometriosis in the real world by considering their symptoms and the diagnostic process in their healthcare setting.

Generalizability of randomized controlled trials in heart failure with reduced ejection fraction.

Background: Heart failure (HF) trials have stringent inclusion and exclusion criteria, but limited data exist regarding generalizability of trials. We compared patient characteristics and outcomes between patients with HF and reduced ejection fraction (HFrEF) in trials and observational registries.

Methods And Results: Individual patient data for 16 922 patients from five randomized clinical trials and 46 914 patients from two HF registries were included.

Clinical Trials Impacted by the COVID-19 Pandemic: Adaptive Designs to the Rescue?

Very recently the new pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified and the coronavirus disease 2019 (COVID-19) declared a pandemic by the World Health Organization. The pandemic has a number of consequences for ongoing clinical trials in non-COVID-19 conditions. Motivated by four current clinical trials in a variety of disease areas we illustrate the challenges faced by the pandemic and sketch out possible solutions including adaptive designs.

Incidence of and risk factors for vaginal cuff dehiscence following total laparoscopic hysterectomy: a monocentric hospital analysis.

Purpose: Vaginal cuff dehiscence (VCD) is one of the major surgical complications following hysterectomy with data on incidence rates varying largely and studies assessing risk factors being sparse with contradictive results. The aim of this study was to assess the incidence rate of and risk factors for VCD in a homogenous cohort of women treated for benign uterine pathologies via total laparoscopic hysterectomy (TLH) with standardized follow-up.

Methods: All patients undergoing TLH at the Department of Gynecology and Obstetrics, Saarland University Hospital between November 2010 and February 2019 were retrospectively identified from a prospectively maintained service database.

The use of external controls: To what extent can it currently be recommended?

With more and better clinical data being captured outside of clinical studies and greater data sharing of clinical studies, external controls may become a more attractive alternative to randomized clinical trials (RCTs). Both industry and regulators recognize that in situations where a randomized study cannot be performed, external controls can provide the needed contextualization to allow a better interpretation of studies without a randomized control. It is also agreed that external controls will not fully replace RCTs as the gold standard for formal proof of efficacy in drug development and the yardstick of clinical research.

Urogynecology in obstetrics: impact of pregnancy and delivery on pelvic floor disorders, a prospective longitudinal observational pilot study.

Purpose: To assess changes in the pelvic floor anatomy that cause pelvic floor disorders (PFDs) in primigravidae during and after pregnancy and to evaluate their impact on women's quality of life (QoL).

Methods: POP-Q and translabial ultrasound examination was performed in the third trimester and 3 months after delivery in a cohort of primigravidae with singleton pregnancy delivering in a tertiary center. Results were analyzed regarding mode of delivery and other pre- and peripartal factors.

Patients' and clinicians' perspectives on item importance, scoring, and clinically meaningful differences for the Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS).

Background: The Endometriosis Symptom Diary (ESD) and Endometriosis Impact Scale (EIS) are patient-reported outcome measures developed to evaluate efficacy in clinical trials and clinical practice. The ESD is a daily electronic diary assessing symptom severity; the EIS is a weekly electronic diary assessing symptom impact. This study explored the importance of symptoms (ESD items) and impacts (EIS domains), perspectives on scoring algorithms, and clinically important difference (CID) thresholds to inform clinical trial score interpretation.

Predicting menstrual bleeding patterns with levonorgestrel-releasing intrauterine systems.

Purpose: To develop a bleeding-pattern prediction model to inform counselling on amount and regularity of bleeding after levonorgestrel-releasing intrauterine system (LNG-IUS) placement.

Materials And Methods: Fixed-cluster and regression-tree models were developed using bleeding data pooled from two clinical trials of LNG-IUSs. Models were trained and cross-validated on LNG-IUS 12 data, then applied to LNG-IUS 20 and LNG-IUS 8 data.

Validation of a menstrual pictogram and a daily bleeding diary for assessment of uterine fibroid treatment efficacy in clinical studies.

Background: To evaluate the psychometric and measurement properties of two patient-reported outcome instruments, the menstrual pictogram superabsorbent polymer-containing version 3 (MP SAP-c v3) and Uterine Fibroid Daily Bleeding Diary (UF-DBD). Test-retest reliability, criterion, construct validity, responsiveness, missingness and comparability of the MP SAP-c v3 and UF-DBD versus the alkaline hematin (AH) method and a patient global impression of severity (PGI-S) were analyzed in post hoc trial analyses.

Results: Analyses were based on data from up to 756 patients.

Using Real-World Data to Predict Clinical and Economic Benefits of a Future Drug Based on its Target Product Profile.

Introduction: For a new drug to be developed, the desired properties are described in a target product profile.

Objective: We propose a framework for using real-world data to measure the disease-specific costs of the current standard of care and then to project the costs of the proposed new product for early data-driven portfolio decisions to select drug candidates for development.

Methods: We sampled from a cohort of patients representing the current standard of care to generate a hypothetical cohort of patients that fits a given target product profile for a new (hypothetical) treatment.

Safety of Dienogest and Other Hormonal Treatments for Endometriosis in Real-World Clinical Practice (VIPOS): A Large Noninterventional Study.

Introduction: Endometriosis is a common gynecologic disease associated with a significant burden on women's health and healthcare systems. Currently approved hormonal treatments for endometriosis can be effective in controlling symptoms, but may have clinically relevant side effects that limit their long-term use. Dienogest 2 mg (Visanne; Bayer AG, Berlin, Germany) is a 19-nortestosterone derivative that significantly reduces menstrual bleeding, dysmenorrhea, premenstrual pain, dyspareunia, and pelvic pain in women with endometriosis.

Is vimentin a potential prognostic factor for patients with triple-negative breast cancer?

Objective: To evaluate the prognostic potential of vimentin, p53, EGFR, CK5/6, CK 14, and CK 17 in patients with triple-negative breast cancer (TNBC).

Material And Methods: Tumor specimens of 60 patients with histologically confirmed TNBC were retrospectively analyzed. Formalin-fixed paraffin-embedded blocks of the tumor tissue were used to prepare tissue microarrays (TMAs).

Cervical and Lower Uterine Parameter Ultrasound and Elastographic Parameters for the Prediction of a Successful Induction of Labor.

Purpose:  The prediction of successful induction of labor (IOL) has been the subject of a series of studies. The predictive role of cervical sonographic and elastographic parameters has been controversially discussed. Lower uterine segment (LUS) thickness and strain values have not been discussed yet in this regard.

Pictorial methods to assess heavy menstrual bleeding in research and clinical practice: a systematic literature review.

Background: Pictorial blood loss assessment charts (PBACs) represent the most widely used method to assess menstrual blood loss (MBL) in clinical trials. The aims of this review were to: (1) determine the diagnostic accuracy of PBACs that have been validated against the reference alkaline hematin technique; (2) categorize the pitfalls of using obsolete and nonvalidated charts; (3) provide guidelines for development of a new PBAC or use of an existing chart to measure MBL in clinical trials; and (4) consider the feasibility of using pictorial charts in primary care.

Methods: A literature review was conducted using Embase and MEDLINE databases.

Impact of body mass index, smoking habit, alcohol consumption, physical activity and parity on disease course of women with triple-negative breast cancer.

Objective: To evaluate the potential impact of body mass index (BMI), smoking habit, alcohol consumption, physical activity and parity on disease course of women with triple-negative breast cancer (TNBC).

Material And Methods: This was a retrospective chart analysis of patients with TNBC. Primary target parameters were overall survival (OS) and disease-free survival (DFS) depending on BMI, smoking habit, alcohol consumption, physical activity and parity.