Determinants of successful lifestyle change during a 6-month preconception lifestyle intervention in women with obesity and infertility.

Purpose: To identify demographic, (bio)physical, behavioral, and psychological determinants of successful lifestyle change and program completion by performing a secondary analysis of the intervention arm of a randomized-controlled trial, investigating a preconception lifestyle intervention.

Methods: The 6-month lifestyle intervention consisted of dietary counseling, physical activity, and behavioral modification, and was aimed at 5-10% weight loss. We operationalized successful lifestyle change as successful weight loss (≥ 5% weight/BMI ≤ 29 kg/m), weight loss in kilograms, a reduction in energy intake, and an increase in physical activity during the intervention program.

Response to HER2 Inhibition in a Patient With Brain Metastasis With EGFR TKI Acquired Resistance and an HER2 Amplification.

A 62-year-old man was referred to our university hospital for treatment of advanced adenocarcinoma of the lung after disease progression on two lines of EGFR TKI and one line of chemotherapy. Fluorescent hybridization analysis upon progression showed an amplification. At our weekly Molecular Tumor Board (MTB), a decision was made to treat this patient with afatinib, which resulted in a partial response.

Prophylactic Cranial Irradiation Versus Observation in Radically Treated Stage III Non-Small-Cell Lung Cancer: A Randomized Phase III NVALT-11/DLCRG-02 Study.

Purpose The purpose of the current study was to investigate whether prophylactic cranial irradiation (PCI) reduces the incidence of symptomatic brain metastases in patients with stage III non-small-cell lung cancer (NSCLC) treated with curative intention. Patients and Methods Patients with stage III NSCLC-staged with a contrast-enhanced brain computed tomography or magnetic resonance imaging-were randomly assigned to either observation or PCI after concurrent/sequential chemoradiotherapy with or without surgery. The primary end point-development of symptomatic brain metastases at 24 months-was defined as one or a combination of key symptoms that suggest brain metastases-signs of increased intracranial pressure, headache, nausea and vomiting, cognitive or affective disturbances, seizures, and focal neurologic symptoms-and magnetic resonance imaging or computed tomography demonstrating the existence of brain metastasis.

New Subsolid Pulmonary Nodules in Lung Cancer Screening: The NELSON Trial.

Introduction: Low-dose computed tomography (LDCT) lung cancer screening is recommended in the United States. While new solid nodules after baseline screening have a high lung cancer probability at small size and require lower size cutoff values than baseline nodules, there only is limited evidence on management of new subsolid nodules.

Methods: Within the Dutch-Belgian randomized controlled LDCT lung cancer screening trial (NELSON), 7557 participants underwent baseline screening between April 2004 and December 2006.

Characteristics of new solid nodules detected in incidence screening rounds of low-dose CT lung cancer screening: the NELSON study.

Purpose: New nodules after baseline are regularly found in low-dose CT lung cancer screening and have a high lung cancer probability. It is unknown whether morphological and location characteristics can improve new nodule risk stratification by size.

Methods: Solid non-calcified nodules detected during incidence screening rounds of the randomised controlled Dutch-Belgian lung cancer screening (NELSON) trial and registered as new or previously below detection limit (15 mm) were included.

Association between periconceptional weight loss and maternal and neonatal outcomes in obese infertile women.

Background: Obesity in women of reproductive age has deleterious effects on reproductive and offspring health. In this study, we aimed to evaluate the association between the magnitude of periconceptional body-mass index (BMI) change and maternal and neonatal outcomes in obese infertile women who participated in the LIFEstyle study. The LIFEstyle study was a randomized controlled trial, evaluating if a six-month lifestyle intervention program prior to infertility treatment in obese infertile women improved birth rates, compared to prompt infertility treatment.

Cost-effectiveness of endobronchial valve treatment in patients with severe emphysema compared to standard medical care.

Background And Objective: Bronchoscopic lung volume reduction using endobronchial valves (EBV) is an effective new treatment option for severe emphysema patients without interlobar collateral ventilation. The objective of this study was to perform an economic evaluation including the costs and cost-effectiveness of EBV treatment compared with standard medical care (SoC) from the hospital perspective in the short term and long term.

Methods: For the short-term evaluation, incremental cost-effectiveness ratios (ICER) were calculated based on the 6-month end point data from the STELVIO randomized trial.

Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly Patients.

The initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [O]HO positron emission tomography-computed tomography (PET-CT).

A Systematic Review and Meta-Analysis on the Strength and Consistency of the Associations between Dupuytren Disease and Diabetes Mellitus, Liver Disease, and Epilepsy.

Background: The role of diabetes mellitus, liver disease, and epilepsy as risk factors for Dupuytren disease remains unclear. In this systematic review and meta-analysis, the strength and consistency of these associations were examined.

Methods: The MEDLINE, EMBASE, and Web of Science databases were searched for articles reporting an association between Dupuytren disease and diabetes mellitus, liver disease, and epilepsy published before September 26, 2016.

Evaluation of biomarkers for treatment selection using individual participant data from multiple clinical trials.

Biomarkers that predict treatment effects may be used to guide treatment decisions, thus improving patient outcomes. A meta-analysis of individual participant data (IPD) is potentially more powerful than a single-study data analysis in evaluating markers for treatment selection. Our study was motivated by the IPD that were collected from 2 randomized controlled trials of hypertension and preeclampsia among pregnant women to evaluate the effect of labor induction over expectant management of the pregnancy in preventing progression to severe maternal disease.

Atmospheric Pressure Variation is a Delayed Trigger for Aneurysmal Subarachnoid Hemorrhage.

Objective: There is an ongoing search for conditions that induce spontaneous subarachnoid hemorrhage (SAH). The seasonal pattern of SAH is shown in a large meta-analysis of the literature, but its explanation remains undecided. There is a clear need for sound meteorologic data to further elucidate the seasonal influence on SAH.

Women, their Offspring and iMproving lifestyle for Better cardiovascular health of both (WOMB project): a protocol of the follow-up of a multicentre randomised controlled trial.

Introduction: Women, their Offspring and iMproving lifestyle for Better cardiovascular health of both (WOMB) project is the follow-up of the LIFEstyle study, a randomised controlled trial in obese infertile women, and investigates the effects of a preconception lifestyle intervention on later health of women (WOMB women) and their children (WOMB kids).

Methods And Analysis: Obese infertile women, aged between 18 and 39 years, were recruited in 23 Dutch fertility clinics between June 2009 and June 2012. The 284 women allocated to the intervention group received a 6-month structured lifestyle programme.

Effect of a lifestyle intervention in obese infertile women on cardiometabolic health and quality of life: A randomized controlled trial.

Background: The prevalence of obesity, an important cardiometabolic risk factor, is rising in women. Lifestyle improvements are the first step in treatment of obesity, but the success depends on factors like timing and motivation. Women are especially receptive to advice about lifestyle before and during pregnancy.

Mutations in EMT-Related Genes in ALK Positive Crizotinib Resistant Non-Small Cell Lung Cancers.

Crizotinib is an effective drug for patients with anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC), but upon treatment, the tumors inevitably become crizotinib resistant in time. The resistance mechanisms are only partly understood. In this study, we aim to identify gene mutations associated with resistance in ALKpositive advanced non-squamous NSCLC treated with crizotinib.

Kidney Function After a Hypertensive Disorder of Pregnancy: A Longitudinal Study.

Background: Registry-based studies report an increased risk for end-stage kidney disease after hypertensive disorders of pregnancy (HDPs). It is unclear whether HDPs lead to an increased incidence of chronic kidney disease (CKD) and/or progression of kidney function decline.

Study Design: Subanalysis of the Prevention of Renal and Vascular Endstage Disease (PREVEND) Study, a Dutch population-based cohort with follow-up of 5 visits approximately 3 years apart.

Phase 2 Study of the HSP-90 Inhibitor AUY922 in Previously Treated and Molecularly Defined Patients with Advanced Non-Small Cell Lung Cancer.

Introduction: In this phase 2 study, we evaluated the activity of AUY922 in pretreated patients with stage IV NSCLC.

Methods: Patients with advanced NSCLC were divided into molecularly defined strata based on mutations in the EGFR gene, the ALK receptor tyrosine kinase gene (ALK), the KRAS gene, or the wild type of all three. All patients must have received more than two prior lines of therapy, except for those in a fifth stratum for a less pretreated EGFR cohort (EGFR<2).

Efficacy of Home Telemonitoring versus Conventional Follow-up: A Randomized Controlled Trial among Teenagers with Inflammatory Bowel Disease.

Background And Aims: Conventional follow-up of teenagers with inflammatory bowel diseases [IBD] is done during scheduled outpatient visits regardless of how well the patient feels. We designed a telemonitoring strategy for early recognition of flares and compared its efficacy with conventional follow-up.

Methods: We used a multicentre randomized trial in patients aged 10-19 years with IBD in clinical remission at baseline.

Resource utilization in lung cancer diagnostic procedures: Current use and budget consequences.

Objectives: The main objective of this study is to determine the current use of lung cancer diagnostic procedures in two large hospitals in the Netherlands, to explore deviations in guideline adherence between the hospitals, and to estimate the budget impact of the diagnostic work-up as well as the over- and underutilization.

Materials & Methods: A state transition model for the diagnostic pathway for lung cancer patients was developed using existing clinical practice guidelines (CPG) combined with a systematic literature. In addition to the CPGs depicting current practice, diagnostic utilization was gathered in two large hospitals representing an academic tertiary care hospital and a large regional teaching hospital for patients, who were selected from the Netherlands cancer registry.

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis.

Study Question: Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment?

Summary Answer: In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose.

What Is Known Already: In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to normalize ovarian response and optimize live birth rates. However, no robust evidence for the (cost-)effectiveness of this practice exists.

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 1: The predicted poor responder.

Study Question: Does an increased FSH dose result in higher cumulative live birth rates in women with a predicted poor ovarian response, apparent from a low antral follicle count (AFC), scheduled for IVF or ICSI?

Summary Answer: In women with a predicted poor ovarian response (AFC < 11) undergoing IVF/ICSI, an increased FSH dose (225/450 IU/day) does not improve cumulative live birth rates as compared to a standard dose (150 IU/day).

What Is Known Already: In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can predict ovarian response to stimulation. The FSH starting dose is often adjusted based on the ORT from the belief that it will improve live birth rates.

Individualized versus standard FSH dosing in women starting IVF/ICSI: an RCT. Part 2: The predicted hyper responder.

Study Question: Does a reduced FSH dose in women with a predicted hyper response, apparent from a high antral follicle count (AFC), who are scheduled for IVF/ICSI lead to a different outcome with respect to cumulative live birth rate and safety?

Summary Answer: Although in women with a predicted hyper response (AFC > 15) undergoing IVF/ICSI a reduced FSH dose (100 IU per day) results in similar cumulative live birth rates and a lower occurrence of any grade of ovarian hyperstimulation syndrome (OHSS) as compared to a standard dose (150 IU/day), a higher first cycle cancellation rate and similar severe OHSS rate were observed.

What Is Known Already: Excessive ovarian response to controlled ovarian stimulation (COS) for IVF/ICSI may result in increased rates of cycle cancellation, the occurrence of OHSS and suboptimal live birth rates. In women scheduled for IVF/ICSI, an ovarian reserve test (ORT) can be used to predict response to COS.

Continued use of afatinib with the addition of cetuximab after progression on afatinib in patients with EGFR mutation-positive non-small-cell lung cancer and acquired resistance to gefitinib or erlotinib.

Objectives: In a phase Ib trial, afatinib plus cetuximab demonstrated promising clinical activity (objective response rate [ORR]: 29%; median progression-free survival [PFS]: 4.7 months) in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) with acquired resistance to erlotinib or gefitinib. Here, a separate cohort exploring afatinib plus cetuximab after progression on afatinib is reported.

Relationship between nodule count and lung cancer probability in baseline CT lung cancer screening: The NELSON study.

Objectives: To explore the relationship between nodule count and lung cancer probability in baseline low-dose CT lung cancer screening.

Materials And Methods: Included were participants from the NELSON trial with at least one baseline nodule (3392 participants [45% of screen-group], 7258 nodules). We determined nodule count per participant.