ECTOPIC trial: The efficacy of flEcainide Compared To metOprolol in reducing Premature ventrIcular Contractions: A randomized open-label crossover study in pediatric patients.

Background: Frequent premature ventricular contractions (PVCs) in children are usually considered benign. Symptoms and left ventricular dysfunction are indications for treatment with antiarrhythmic drugs.

Objective: This study aimed to evaluate the efficacy of flecainide vs metoprolol in reducing PVCs in children.

Total mesorectal excision in MRI-defined low rectal cancer: multicentre study comparing oncological outcomes of robotic, laparoscopic and transanal total mesorectal excision in high-volume centres.

Background: The routine use of MRI in rectal cancer treatment allows the use of a strict definition for low rectal cancer. This study aimed to compare minimally invasive total mesorectal excision in MRI-defined low rectal cancer in expert laparoscopic, transanal and robotic high-volume centres.

Methods: All MRI-defined low rectal cancer operated on between 2015 and 2017 in 11 Dutch centres were included.

Effect of absolute blood volume measurement-guided fluid management on the incidence of intradialytic hypotension-associated events: a randomised controlled trial.

Background: Ultrafiltration to target weight during haemodialysis is complicated by intradialytic hypotension-associated adverse events (IHAAEs) in 10-30% of dialysis treatments. IHAAEs are caused by critical reductions in absolute blood volume (ABV), due to the interaction of ultrafiltration, refill and compensatory mechanisms. Non-randomised studies have suggested that ABV-guided treatment, using an indicator dilution technique employing the blood volume monitor on the dialysis machine, could reduce the incidence of IHAAEs.

Prediction Under Interventions: Evaluation of Counterfactual Performance Using Longitudinal Observational Data.

Predictions under interventions are estimates of what a person's risk of an outcome would be if they were to follow a particular treatment strategy, given their individual characteristics. Such predictions can give important input to medical decision-making. However, evaluating the predictive performance of interventional predictions is challenging.

Cumulative incidence and risk factors for cutaneous squamous cell carcinoma metastases in organ transplant recipients: The Skin Care in Organ Transplant Patients in Europe-International Transplant Skin Cancer Collaborative metastases study, a prospective multicenter study.

Introduction: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors.

Methods: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected.

Darbepoetin alfa to reduce transfusion episodes in infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions in the Netherlands: an open-label, single-centre, phase 2, randomised, controlled trial.

Background: Up to 88% of infants with haemolytic disease of the fetus and newborn who are treated with intrauterine transfusions require erythrocyte transfusions after birth. We aimed to investigate the effect of darbepoetin alfa on the prevention of postnatal anaemia in infants with haemolytic disease of the fetus and newborn.

Methods: We conducted an open-label, single-centre, phase 2 randomised controlled trial to evaluate the effect of darbepoetin alfa on the number of erythrocyte transfusions in infants with haemolytic disease of the fetus and newborn.

Allogeneic Serum Eye Drops: A Randomized Clinical Trial to Evaluate the Clinical Effectiveness of Two Drop Sizes.

Introduction: Allogeneic serum from blood donors is starting to be used to treat patients with dry eye disease (DED). However, the optimal dose is not known. We therefore aimed to evaluate the clinical efficaciousness and user-friendliness of micro-sized versus conventional-sized allogeneic serum eye drops (SEDs).

A Cost Overview of Minimally Invasive Total Mesorectal Excision in Rectal Cancer Patients: A Population-based Cohort in Experienced Centres.

Background: Total mesorectal excision has been the gold standard for the operative management of rectal cancer. The most frequently used minimally invasive techniques for surgical resection of rectal cancer are laparoscopic, robot-assisted, and transanal total mesorectal excision. As studies comparing the costs of the techniques are lacking, this study aims to provide a cost overview.

Sentinel lymph node procedure in early-stage vulvar cancer: Correlation of lymphoscintigraphy with surgical outcome and groin recurrence.

Introduction: In early-stage vulvar squamous cell carcinoma (VSCC) a sentinel lymph node (SLN) procedure is regarded successful if at least one SLN is removed with minimal residual radioactivity. An inguinofemoral lymphadenectomy is considered if not all SLNs visualized on lymphoscintigraphy can be found, with subsequent increased morbidity. We correlated lymphoscintigraphy findings with surgical outcome and groin recurrence with focus on number of SLNs found.

Cost-effectiveness of general practitioner- versus surgeon-led colon cancer survivorship care: an economic evaluation alongside a randomised controlled trial.

Purpose: The aim of this study is to assess cost-effectiveness of general practitioner (GP) versus surgeon-led colon cancer survivorship care from a societal perspective.

Methods: We performed an economic evaluation alongside the I CARE study, which included 303 cancer patients (stages I-III) who were randomised to survivorship care by a GP or surgeon. Questionnaires were administered at baseline, 3-, 6-, 12-, 24- and 36-months.

Tell me what you want, what you really really want: Estimands in observational pharmacoepidemiologic comparative effectiveness and safety studies.

Purpose: Ideally, the objectives of a pharmacoepidemiologic comparative effectiveness or safety study should dictate its design and data analysis. This paper discusses how defining an estimand is instrumental to this process.

Methods: We applied the ICH-E9 (Statistical Principles for Clinical Trials) R1 addendum on estimands - which originally focused on randomized trials - to three examples of observational pharmacoepidemiologic comparative effectiveness and safety studies.

Birthweight of children with isolated congenital heart disease-A sibling analysis study.

Objective: Congenital heart disease (CHD) is associated with decreased birthweight (BW) compared to population-based references. The aim of this study was to compare the BW of isolated CHD cases to their siblings, thus controlling for unknown and unmeasured confounders within the family.

Methods: All isolated CHD cases in the Leiden University Medical Center were included (2002-2019).

Assessing Performance and Clinical Usefulness in Prediction Models With Survival Outcomes: Practical Guidance for Cox Proportional Hazards Models.

Risk prediction models need thorough validation to assess their performance. Validation of models for survival outcomes poses challenges due to the censoring of observations and the varying time horizon at which predictions can be made. This article describes measures to evaluate predictions and the potential improvement in decision making from survival models based on Cox proportional hazards regression.

Comparison of three-year oncological results after restorative low anterior resection, non-restorative low anterior resection and abdominoperineal resection for rectal cancer.

Introduction: Oncological outcome might be influenced by the type of resection in total mesorectal excision (TME) for rectal cancer. The aim was to see if non-restorative LAR would have worse oncological outcome. A comparison was made between non-restorative low anterior resection (NRLAR), restorative low anterior resection (RLAR) and abdominoperineal resection (APR).

Development of the OPAL prediction model for prediction of live birth in couples with recurrent pregnancy loss: protocol for a prospective and retrospective cohort study in the Netherlands.

Introduction: Recurrent pregnancy loss (RPL) is defined as the loss of two or more conceptions before 24 weeks gestation. Despite extensive diagnostic workup, in only 25%-40% an underlying cause is identified. Several factors may increase the risk for miscarriage, but the chance of a successful pregnancy is still high.

Outpatient convalescent plasma therapy for high-risk patients with early COVID-19: a randomized placebo-controlled trial.

Objectives: The potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine the effectiveness of CP therapy in improving the disease course of COVID-19 among high-risk outpatients.

Methods: A multicentre, double-blind randomized trial was conducted comparing 300 mL of CP with non-CP.

Predicting cumulative live birth for couples beginning their second complete cycle of in vitro fertilization treatment.

Study Question: Can we develop an IVF prediction model to estimate individualized chances of a live birth over multiple complete cycles of IVF in couples embarking on their second complete cycle of treatment?

Summary Answer: Yes, our prediction model can estimate individualized chances of cumulative live birth over three additional complete cycles of IVF.

What Is Known Already: After the completion of a first complete cycle of IVF, couples who are unsuccessful may choose to undergo further treatment to have their first child, while those who have had a live birth may decide to have more children. Existing prediction models can estimate the overall chances of success in couples before commencing IVF but are unable to revise these chances on the basis of the couple's response to a first treatment cycle in terms of the number of eggs retrieved and pregnancy outcome.

The Disconnect Between Development and Intended Use of Clinical Prediction Models for Covid-19: A Systematic Review and Real-World Data Illustration.

Background: The SARS-CoV-2 pandemic has boosted the appearance of clinical predictions models in medical literature. Many of these models aim to provide guidance for decision making on treatment initiation. Special consideration on how to account for post-baseline treatments is needed when developing such models.

Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients.

Unlabelled: Data on convalescent plasma (CP) treatment in COVID-19 outpatients are scarce. We aimed to assess whether CP administered during the first week of symptoms reduced the disease progression or risk of hospitalization of outpatients. Two multicenter, double-blind randomized trials (NCT04621123, NCT04589949) were merged with data pooling starting when <20% of recruitment target was achieved.

Short-term and long-term prognostic value of histological response and intensified chemotherapy in osteosarcoma: a retrospective reanalysis of the BO06 trial.

Objectives: Cure rate models accounting for cured and uncured patients, provide additional insights into long and short-term survival. We aim to evaluate the prognostic value of histological response and chemotherapy intensification on the cure fraction and progression-free survival (PFS) for the uncured patients.

Design: Retrospective analysis of a randomised controlled trial, MRC BO06 (EORTC 80931).

Birthweight and isolated congenital heart defects - A systematic review and meta-analysis.

Background: Birthweight (BW) is an important prognostic factor in newborns with congenital heart defects (CHD).

Objectives: To give an overview of the literature on BW z-score in children with isolated CHD.

Search Strategy: A systematic search was performed on isolated CHD and BW in PubMed, Embase, Web of Science, COCHRANE Library and Emcare.