Lipid levels and risk of venous thrombosis: results from the MEGA-study.

The relationship between lipid levels and risk of venous thrombosis is not well established. We aimed to assess the association between several lipids and risk of venous thrombosis using data from a population-based case-control study, and to evaluate the underlying mechanism, considering confounding by common risk factors and mediation via hemostatic factors and C-reactive protein. From the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study, 2234 patients with a first venous thrombosis and 2873 controls were included.

First-Line Palliative HER2-Targeted Therapy in HER2-Positive Metastatic Breast Cancer Is Less Effective After Previous Adjuvant Trastuzumab-Based Therapy.

Background: Survival of patients with human epidermal growth receptor 2 (HER2)-positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [OS] and time to next treatment [TNT]) in MBC patients pretreated with trastuzumab in the adjuvant setting (TP-group) compared with trastuzumab-naïve patients (TN-group) in order to investigate the possibility of trastuzumab resistance.

Patients And Methods: Patients treated with first-line HER2-targeted-containing chemotherapy were eligible for the study.

Cortical hyperexcitability and disease spread in amyotrophic lateral sclerosis.

Background And Purpose: Amyotrophic lateral sclerosis (ALS) is characterized by focal disease onset with a predominantly contiguous pattern of disease spread. The pathophysiological mechanisms underlying disease progression in ALS have not been elucidated. Given that cortical hyperexcitability has been identified as an important pathogenic mechanism in ALS, the aim of the present study was to determine whether changes in cortical function could mediate disease spread in ALS.

Iridium-catalysed asymmetric allylic alkylation of benzofuran γ-lactones followed by heteroaromatic Cope rearrangement: study of an unusual reaction sequence.

The iridium-catalysed asymmetric allylic alkylation of γ-lactones produces an all-carbon quaternary stereocentre substituted by an allyl and a benzofuran. The resulting 1,5-hexadienes were found to be excellent substrates for an unusual heteroaromatic Cope rearrangement. We describe here the first insight into the synthetic outcome of this intriguing reaction sequence.

Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans.

Objective: Mendelian randomization studies revealed a causal role for remnant cholesterol in cardiovascular disease. Remnant particles accumulate in the arterial wall, potentially propagating local and systemic inflammation. We evaluated the impact of remnant cholesterol on arterial wall inflammation, circulating monocytes, and bone marrow in patients with familial dysbetalipoproteinemia (FD).

Trastuzumab in combination with weekly paclitaxel and carboplatin as neo-adjuvant treatment for HER2-positive breast cancer: The TRAIN-study.

Aim: To determine the efficacy and safety of an anthracycline-free neo-adjuvant regimen consisting of weekly paclitaxel, carboplatin and trastuzumab in HER2-positive breast cancer.

Patients And Methods: Patients with stage II or III HER2-positive breast cancer received weekly paclitaxel ([P], 70 mg/m), trastuzumab ([T], 2 mg/kg, loading dose 4 mg/kg) and carboplatin ([C], AUC = 3 mg ml min) for 24 weeks. In weeks 7, 8, 15, 16, 23 and 24, trastuzumab was administered without chemotherapy.

Thyroid Signaling, Insulin Resistance, and 2 Diabetes Mellitus: A Mendelian Randomization Study.

Context: Increasing evidence suggests an association between thyroid-stimulating hormone (TSH), free thyroxine (fT4), and deiodinases with insulin resistance and type 2 diabetes mellitus (T2D).

Objective: We examined whether TSH and fT4 levels and deiodinases are causally associated with insulin resistance and T2D, using Mendelian randomization.

Methods: We selected 20 genetic variants for TSH level and four for fT4 level (identified in a genome-wide association study (GWAS) meta-analysis of European-ancestry cohorts) as instrumental variables for TSH and fT4 levels, respectively.

Thirty-Minute Office Blood Pressure Monitoring in Primary Care.

Purpose: Automated office blood pressure monitoring during 30 minutes (OBP30) may reduce overtreatment of patients with white-coat hypertension in primary health care. OBP30 results approximate those of ambulatory blood pressure monitoring, but OBP30 is much more convenient. In this study, we compared OBP30 with routine office blood pressure (OBP) readings for different indications in primary care and evaluated how OBP30 influenced the medication prescribing of family physicians.

Exploring the role of testosterone in the cerebellum link to neuroticism: From adolescence to early adulthood.

Previous research has found an association between a smaller cerebellar volume and higher levels of neuroticism. The steroid hormone testosterone reduces stress responses and the susceptibility to negative mood. Together with in vitro studies showing a positive effect of testosterone on cerebellar gray matter volumes, we set out to explore the role of testosterone in the relation between cerebellar gray matter and neuroticism.

EMA and EFSA Joint Scientific Opinion on measures to reduce the need to use antimicrobial agents in animal husbandry in the European Union, and the resulting impacts on food safety (RONAFA).

EFSA and EMA have jointly reviewed measures taken in the EU to reduce the need for and use of antimicrobials in food-producing animals, and the resultant impacts on antimicrobial resistance (AMR). Reduction strategies have been implemented successfully in some Member States. Such strategies include national reduction targets, benchmarking of antimicrobial use, controls on prescribing and restrictions on use of specific critically important antimicrobials, together with improvements to animal husbandry and disease prevention and control measures.

Pharmaceutical pictograms for low-literate patients: Understanding, risk of false confidence, and evidence-based design strategies.

Objective: This study aims to (1) evaluate ten pharmaceutical pictograms for low-literate patients on understandability, (2) assess the risk of false confidence in understanding, and (3) identify how the design can be improved to increase understandability.

Methods: Interviews were conducted with n=197 pharmacy visitors in the Netherlands. Additional qualitative discussions were held with n=30 adequately and n=25 low-literate participants (assessed with REALM-D).

Physiological processes influencing motor-evoked potential duration with voluntary contraction.

Voluntary contraction leads to facilitation of motor-evoked potentials (MEPs) producing greater amplitude, shorter onset latency, and prolonged duration of the electromyography potential. Whereas hyperexcitability of spinal motoneurons and changes in descending corticospinal volleys have been proposed as putative mechanisms for changes in MEP amplitude and onset latency, a contribution of propriospinal interneurons, exerting modulatory effects on α-motoneurons, has been proposed as a potential explanation for prolongation of MEP duration. The aim of the present study is to gain further insight into the physiological processes underlying changes in MEP duration.

Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists.

Background: Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients.

Objectives: To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations.

Everolimus in Patients With Advanced Follicular-Derived Thyroid Cancer: Results of a Phase II Clinical Trial.

Background: Mammalian target of rapamycin (mTOR) upregulation has been reported to be involved in the pathogenesis of thyroid tumors, and treatment with the mTOR inhibitor everolimus has shown promising results in endocrine tumors. We conducted a prospective phase II clinical trial to determine the efficacy and safety of everolimus in patients with advanced follicular-derived thyroid cancer.

Patients And Methods: Twenty-eight patients with progressive metastatic or locally advanced radioactive refractory differentiated thyroid cancer and 7 patients with anaplastic thyroid cancer were included and received everolimus 10 mg orally once daily.

Recent Progress Toward the Synthesis of Trifluoromethyl- and Difluoromethyl-Substituted Cyclopropanes.

This Minireview describes recent advances toward the synthesis of trifluoromethyl- and difluoromethyl-substituted cyclopropanes. Synthetic methodologies using [2+1] cycloaddition, ring-contraction, and ring-closure cyclopropanations since 2010 are reported.

Loss of placental thrombomodulin in oocyte donation pregnancies.

Objective: To investigate whether thrombomodulin dysregulation is involved in the development of preeclampsia after oocyte donation (OD). Women who become pregnant after OD are prone to develop preeclampsia, a syndrome characterized by an aberrant immunologic response, hypercoagulability, and endothelial dysfunction. A mediator of inflammation and coagulation is thrombomodulin, which has a possible role to play in this syndrome.

Cognitive Impairment in a Subset of Breast Cancer Patients After Systemic Therapy-Results From a Longitudinal Study.

Context: Studies indicate adverse effects of breast cancer (BC) and cancer treatment on cognitive function.

Objectives: To investigate the effects of systemic treatment on cognitive performance in BC patients.

Methods: Participants were BC patients scheduled to receive systemic treatment (BC + SYST; n = 31), or no systemic treatment (BC; n = 24) and no-cancer (NC) controls (n = 33).

Disclosing the Uncertainty Associated with Prognostic Estimates in Breast Cancer.

Background: Treatment decision making is often guided by evidence-based probabilities, which may be presented to patients during consultations. These probabilities are intrinsically imperfect and embody 2 types of uncertainties: aleatory uncertainty arising from the unpredictability of future events and epistemic uncertainty arising from limitations in the reliability and accuracy of probability estimates. Risk communication experts have recommended disclosing uncertainty.

Low literacy and written drug information: information-seeking, leaflet evaluation and preferences, and roles for images.

Background Low-literate patients are at risk to misinterpret written drug information. For the (co-) design of targeted patient information, it is key to involve this group in determining their communication barriers and information needs. Objective To gain insight into how people with low literacy use and evaluate written drug information, and to identify ways in which they feel the patient leaflet can be improved, and in particular how images could be used.

Enlarged NT (≥3.5 mm) in the first trimester - not all chromosome aberrations can be detected by NIPT.

Background: Since non-invasive prenatal testing (NIPT) in maternal blood became available, we evaluated which chromosome aberrations found in our cohort of fetuses with an enlarged NT in the first trimester of pregnancy (tested with SNP microarray) could be detected by NIPT as well.

Method: 362 fetuses were referred for cytogenetic testing due to an enlarged NT (≥3.5 mm).

Efficient expression of functional human coagulation factor IX in stably-transfected Drosophila melanogaster S2 cells; comparison with the mammalian CHO system.

Objective: To compare stably-transfected Drosophila melanogaster S2 and mammalian Chinese hamster ovary (CHO) cells for the expression and secretion efficiency of biologically-active human coagulation factor IX (hFIX).

Result: Selection of an hFIX-expressing cell line derived from stably-transfected S2 cells was performed over 2 weeks, while the same procedure required 2 months for stably-transfected CHO cells. Furthermore, the selected S2 cell line was superior in producing of total hFIX protein (70 % increase), biologically-active hFIX (35 % increase), and specific hFIX activity (20 % increase) relative to the selected CHO cell line.

Decolonisation of meticillin-resistant Staphylococcus aureus (MRSA) carriage in adopted children with cleft lip and palate.

This study aimed to determine the percentage success and to investigate influencing factors of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation treatment in children with cleft lip and/or palate (CLP) who are adopted to The Netherlands. This was a historic cohort study in nine Dutch hospitals with a CLP treatment centre of children who were adopted from abroad in 2005-2012 who had CLP and MRSA carriage upon arrival in The Netherlands. A total of 55 adopted children with CLP and MRSA carriage were eligible for the study.

Trafficking in Human Beings for the Purpose of Organ Removal and the Ethical and Legal Obligations of Healthcare Providers.

Physicians and other health care professionals seem well placed to play a role in the monitoring and, perhaps, in the curtailment of the trafficking in human beings for the purpose of organ removal. They serve as important sources of information for patients and may have access to information that can be used to gain a greater understanding of organ trafficking networks. However, well-established legal and ethical obligations owed to their patients can create challenging policy tensions that can make it difficult to implement policy action at the level of the physician/patient.