Spillover effects of supplementary on basic health insurance: evidence from the Netherlands

Like many other countries, the Netherlands has a health insurance system that combines mandatory basic insurance with voluntary supplementary insurance. Both types of insurance are founded on different principles. Since basic and supplementary insurance are sold by the same health insurers, both markets may interact. This paper examines to what extent basic and supplementary insurance are linked to each other and whether these links generate spillover effects of supplementary on basic insurance. Our analysis is based on an investigation into supplementary health insurance contracts, underwriting procedures and annual surveys among 1,700–2,100 respondents over the period 2006–2009. We find that health insurers increasingly use a variety of strategies to enforce a joint purchase of basic and supplementary health insurance. Despite incentives for health insurers to use supplementary insurance as a tool for risk selection in basic insurance, we find limited evidence of supplementary insurance being used this way. Only a minority of health insurers uses health questionnaires when people apply for supplementary coverage. Nevertheless, we find that an increasing proportion of high-risk individuals believe that insurers would not be willing to offer them another supplementary insurance contract. We discuss several strategies to prevent or to counteract the observed negative spillover effects of supplementary insurance

WDR5, BRCA1, and BARD1 Co-regulate the DNA Damage Response and Modulate the Mesenchymal-to-Epithelial Transition during Early Reprogramming.

Differentiated cells are epigenetically stable, but can be reprogrammed to pluripotency by expression of the OSKM transcription factors. Despite significant effort, relatively little is known about the cellular requirements for reprogramming and how they affect the properties of induced pluripotent stem cells. We have performed high-content screening with small interfering RNAs targeting 300 chromatin-associated factors and extracted colony-level quantitative features. This revealed five morphological phenotypes in early reprogramming, including one displaying large round colonies exhibiting an early block of reprogramming. Using RNA sequencing, we identified transcriptional changes associated with these phenotypes. Furthermore, double knockdown epistasis experiments revealed that BRCA1, BARD1, and WDR5 functionally interact and are required for the DNA damage response. In addition, the mesenchymal-to-epithelial transition is affected in Brca1, Bard1, and Wdr5 knockdowns. Our data provide a resource of chromatin-associated factors in early reprogramming and underline colony morphology as an important high-dimensional readout for reprogramming quality

Balmer Filaments in Tycho's Supernova Remnant: An Interplay between Cosmic-ray and Broad-neutral Precursors

We present H alpha spectroscopic observations and detailed modeling of the Balmer filaments in the supernova remnant (SNR) Tycho (SN 1572). We used GH alpha FaS (Galaxy H alpha Fabry-Perot Spectrometer) on the William Herschel Telescope with a 3'.4 x 3'.4 field of view, 0 ''.2 pixel scale, and sigma(instr) = 8.1 km s(-1) resolution at 1 '' seeing for similar to 10. hr, resulting in 82 spatial-spectral bins that resolve the narrow H alpha line in the entire SN 1572 northeastern rim. For the first time, we can therefore mitigate artificial line broadening from unresolved differential motion and probe H alpha emission parameters in varying shock and ambient medium conditions. Broad H alpha line remains unresolved within spectral coverage of 392 km s-1. We employed Bayesian inference to obtain reliable parameter confidence intervals and to quantify the evidence for models with multiple line components. The median H alpha narrow-line (NL) FWHM of all bins and models is W-NL = (54.8 +/- 1.8) km s(-1) at the 95% confidence level, varying within [35, 72] km s(-1) between bins and clearly broadened compared to the intrinsic (thermal) approximate to 20 km s(-1). Possible line splits are accounted for, significant in approximate to 18% of the filament, and presumably due to remaining projection effects. We also find widespread evidence for intermediate-line emission of a broad-neutral precursor, with a median W-IL =(180 +/- 14) km s(-1) (95% confidence). Finally, we present a measurement of the remnant's systemic velocity, V-LSR = -34 km s(-1), and map differential line-of-sight motions. Our results confirm the existence and interplay of shock precursors in Tycho's remnant. In particular, we show that suprathermal NL emission is near-universal in SN 1572, and that, in the absence of an alternative explanation, collisionless SNR shocks constitute a viable acceleration source for Galactic TeV cosmic-ray protons

Renal artery stenosis-when to screen, what to stent?

Renal artery stensosis (RAS) continues to be a problem for clinicians, with no clear consensus on how to investigate and assess the clinical significance of stenotic lesions and manage the findings. RAS caused by fibromuscular dysplasia is probably commoner than previously appreciated, should be actively looked for in younger hypertensive patients and can be managed successfully with angioplasty. Atheromatous RAS is associated with increased incidence of cardiovascular events and increased cardiovascular mortality, and is likely to be seen with increasing frequency. Evidence from large clinical trials has led clinicians away from recommending interventional revascularisation towards aggressive medical management. There is now interest in looking more closely at patient selection for intervention, with focus on intervening only in patients with the highest-risk presentations such as flash pulmonary oedema, rapidly declining renal function and severe resistant hypertension. The potential benefits in terms of improving hard cardiovascular outcomes may outweigh the risks of intervention in this group, and further research is needed

High susceptibility of c-KIT+CD34+ precursors to prolonged doxorubicin exposure interferes with Langerhans cell differentiation in a human cell line model

As neoadjuvant and adjuvant chemotherapy schedules often consist of multiple treatment cycles over relatively long periods of time, it is important to know what effects protracted drug administration can have on the immune system. Here, we studied the long-term effects of doxorubicin on the capacity of dendritic cell (DC) precursors to differentiate into a particular DC subset, the Langerhans cells (LC). In order to achieve high telomerase activity as detected in hematological stem cells, precursor cells from the acute-myeloid leukemia (AML)-derived cell line MUTZ3 were stably transduced with human telomerase reverse transcriptase (hTERT) to facilitate their growth potential, while preventing growth, and drug-induced senescence, and preserving their unique capacity for cytokine-dependent DC and LC differentiation. The hTERT-MUTZ3 cells were selected with increasing concentrations of the anthracyclin doxorubicin. After 1–2 months of selection with 30–90 nM doxorubicin, the cells completely lost their capacity to differentiate into LC. This inhibition turned out to be reversible, as the cells slowly regained their capacity to differentiate after a 3- to 4-month drug-free period and with this became capable again of priming allogeneic T cells. Of note, the loss and gain of this capacity to differentiate coincided with the loss and gain of a subpopulation within the CD34+ proliferative compartment with surface expression of the stem cell factor receptor (SCF-R/CD117/c-Kit). These data are in favor of cytostatic drug-free intervals before applying autologous DC-based vaccination protocols, as specific DC precursors may need time to recover from protracted chemotherapy treatment and re-emerge among the circulating CD34+ hematopoietic stem and precursor cells

Educational paper: Primary antibody deficiencies

Primary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA and IgG subclass deficiencies to the severe congenital agammaglobulinemias, in which the antibody production of all immunoglobulin isotypes is severely decreased. Apart from recurrent respiratory tract infections, PADs are associated with a wide range of other clinical complications. This review will describe the pathophysiology, diagnosis, and treatment of the different PADs

Educational paper: The expanding clinical and immunological spectrum of severe combined immunodeficiency

Severe combined immunodeficiency (SCID) is one of the most severe forms of primary immunodeficiency characterized by absence of functional T lymphocytes. It is a paediatric emergency, which is life-threatening when recognized too late. The clinical presentation varies from the classical form of SCID through atypical SCID to Omenn syndrome. In addition, there is a considerable immunological variation, which can hamper the diagnosis. In this educational review, we describe the immunopathological background, clinical presentations and diagnostic process of SCID, as well as the therapeutic possibilities

Case-finding of dementia in general practice and effects of subsequent collaborative care; design of a cluster RCT

<p>Abstract</p> <p>Background</p> <p>In the primary care setting, dementia is often diagnosed relatively late in the disease process. Case finding and proactive collaborative care may have beneficial effects on both patient and informal caregiver by clarifying the cause of cognitive decline and changed behaviour and by enabling support, care planning and access to services.</p> <p>We aim to improve the recognition and diagnosis of individuals with dementia in general practice. In addition to this diagnostic aim, the effects of case finding and subsequent care on the mental health of individuals with dementia and the mental health of their informal carers are explored.</p> <p>Methods and design</p> <p>Design: cluster randomised controlled trial with process evaluation.</p> <p>Participants: 162 individuals ≥ 65 years, in 15 primary care practices, in whom GPs suspect cognitive impairment, but without a dementia diagnosis.</p> <p>Intervention; case finding and collaborative care: 2 trained practice nurses (PNs) invite all patients with suspected cognitive impairment for a brief functional and cognitive screening. If the cognitive tests are supportive of cognitive impairment, individuals are referred to their GP for further evaluation. If dementia is diagnosed, a comprehensive geriatric assessment takes place to identify other relevant geriatric problems that need to be addressed. Furthermore, the team of GP and PN provide information and support.</p> <p>Control: GPs provide care and diagnosis as usual.</p> <p>Main study parameters: after 12 months both groups are compared on: 1) incident dementia (and MCI) diagnoses and 2) patient and caregiver quality of life (QoL-AD; EQ5D) and mental health (MH5; GHQ 12) and caregiver competence to care (SSCQ). The process evaluation concerns facilitating and impeding factors to the implementation of this intervention. These factors are assessed on the care provider level, the care recipient level and on the organisational level.</p> <p>Discussion</p> <p>This study will provide insight into the diagnostic yield and the clinical effects of case finding and collaborative care for individuals with suspected cognitive impairment, compared to usual care. A process evaluation will give insight into the feasibility of this intervention.</p> <p>The first results are expected in the course of 2013.</p> <p>Trial registration</p> <p>NTR3389</p