Written survey on recently deceased patients in germany and switzerland: how do general practitioners see their role?

BACKGROUND General practitioners (GPs) play an important role in end-of-life care due to their proximity to the patient's dwelling-place and their contact to relatives and other care providers. METHODS In order to get a better understanding of the role which the GP sees him- or herself as playing in end-of-life care and which care their dying patients get, we conducted this written survey. It asked questions about the most recently deceased patient of each physician. The questionnaire was sent to 1,201 GPs in southern North Rhine-Westphalia (Germany) and the Canton of Bern (Switzerland). RESULTS Response rate was 27.5 % (n = 330). The average age of responding physicians was 54.5 years (range: 34-76; standard derivation: 7.4), 68 % of them were male and 45 % worked alone in their practice. Primary outcome measures of this observational study are the characteristics of recently deceased patients as well as their care and the involvement of other professional caregivers. Almost half of the most recently deceased patients had cancer. Only 3 to 16 % of all deceased suffered from severe levels of pain, nausea, dyspnea or emesis. More than 80 % of the doctors considered themselves to be an indispensable part of their patient's end-of-life care. Almost 90 % of the doctors were in contact with the patient's family and 50 % with the responsible nursing service. The majority of the GPs had taken over the coordination of care and cooperation with other attending physicians. CONCLUSION The study confirms the relevance of caring for dying patients in GPs work and provides an important insight into their perception of their own role.

Three-year efficacy and safety of new- versus early-generation drug-eluting stents for unprotected left main coronary artery disease insights from the ISAR-LEFT MAIN and ISAR-LEFT MAIN 2 trials.

BACKGROUND In percutaneous coronary intervention (PCI) patients new-generation drug-eluting stent (DES) has reduced adverse events in comparison to early-generation DES. The aim of the current study was to investigate the long-term clinical efficacy and safety of new-generation DES versus early-generation DES for PCI of unprotected left main coronary artery (uLMCA) disease. METHODS The patient-level data from the ISAR-LEFT MAIN and ISAR-LEFT MAIN 2 randomized trials were pooled. The clinical outcomes of PCI patients assigned to new-generation DES (everolimus- or zotarolimus-eluting stent) versus early-generation DES (paclitaxel- or sirolimus-eluting stent) were studied. The primary endpoint was the composite of death, myocardial infarction (MI), target lesion revascularization and stroke (MACCE, major adverse cardiac and cerebrovascular event). RESULTS In total, 1257 patients were available. At 3 years, the risk of MACCE was comparable between patients assigned to new-generation DES or early-generation DES (28.2 versus 27.5 %, hazard ratio-HR 1.03, 95 % confidence intervals-CI 0.83-1.26; P = 0.86). Definite/probable stent thrombosis was low and comparable between new-generation DES and early-generation DES (0.8 versus 1.6 %, HR 0.52, 95 % CI 0.18-1.57; P = 0.25); in patients treated with new-generation DES no cases occurred beyond 30 days. Diabetes increased the risk of MACCE in patients treated with new-generation DES but not with early-generation DES (P interaction = 0.004). CONCLUSIONS At 3-year follow-up, a PCI with new-generation DES for uLMCA disease shows comparable efficacy to early-generation DES. Rates of stent thrombosis were low in both groups. Diabetes significantly impacts the risk of MACCE at 3 years in patients treated with new-generation DES for uLMCA disease. ClinicalTrials.gov Identifiers: NCT00133237; NCT00598637.

Equilibria with Local Governments and Commuting: Income Sorting vs. Income Mixing

Tiebout's (1956) model of fiscal competition suggests income sorting between jurisdictions while the Alonso (1964), Mills (167) and Muth (1969) model of the monocentric city suggests income sorting over space. However, strict income sorting is not empirically observed. We add fiscal competition to the spatial model by considering a circular inner city surrounded by a suburb. The fiscal difference between the jurisdictions and the commuting advantage of locations closer to the city center are capitalized into house prices. In addition to the traditional equilibrium with income sorting, there are equilibria with income mixing - both across jurisdictions and across space.

Elucidating the IGFBP2 signaling pathway in glioma development and progression

Diffuse gliomas are highly lethal central nervous system malignancies which, unfortunately, are the most common primary brain tumor and also the least responsive to the very few therapeutic modalities currently available to treat them. IGFBP2 is a newly recognized oncogene that is operative in multiple cancer types, including glioma, and shows promise for a targeted therapeutic approach. Elevated IGFBP2 expression is present in high-grade glioma and correlates with poor survival. We have previously demonstrated that IGFBP2 induces glioma development and progression in a spontaneous glioma mouse model, which highlighted its significance and potential for future therapy. However, we did not yet know the key physiological pathways associated with this newly characterized oncogene. We first evaluated human glioma genomics data harnessed from the publicly available Rembrandt source to identify major pathways associated with IGFBP2 expression. Integrin and ILK, among other cell migration and invasion-related pathways, were the most prominently associated. We confirmed that these pathways are regulated by IGFBP2 in glioma cells lines, and demonstrated that 1) IGFBP2 activates integrin α5β1, leading to the activation of key pathways important in glioma; 2) IGFBP2 mediates cell migration pathways through ILK; and 3) IGFBP2 activates NF-kB via an integrin α5 interaction. We then sought to determine whether this was a physiologically active signaling pathway in vivo by assessing its ability to induce glioma progression in the RCAS/tv-a spontaneous glioma mouse model. We found that ILK is a key downstream mediator of IGFBP2 that is required for the induction of glioma progression. Most significantly, a genetic therapeutic approach revealed that perturbation of any point in the pathway thwarted tumor progression, providing strong evidence that targeting the key players could potentially produce a significant benefit for human glioma patients. The elucidation of this signaling pathway is a critical step, since efforts to create a small molecule drug targeting IGFBP2 have so far not been successful, but a number of inhibitors of the other pathway constituents, including ILK, integrin and NF-kB, have been developed.

Magnetostratigraphy of ODP Leg 207 sediments

Ocean Drilling Program (ODP) Sites 1257-1261 recovered thick sections of Upper Cretaceous-Eocene oceanic sediments on Demerara Rise off the east coast of Surinam and French Guiana, South America. Paleomagnetic and rock magnetic measurements of ~800 minicores established a high-resolution composite magnetostratigraphy spanning most of the Maastrichtian-Eocene. Magnetic behavior during demagnetization varied among lithologies, but thermal demagnetization steps >200°C were generally successful in removing present-day normal polarity overprints and a downward overprint induced during the ODP coring process. Characteristic remanent magnetizations and associated polarity interpretations were generally assigned to directions observed at 200°-400°C, and the associated polarity interpretations were partially based on whether the characteristic direction was aligned or apparently opposite to the low-temperature "north-directed" overprint. Biostratigraphy and polarity patterns constrained assignment of polarity chrons. The composite sections have a complete polarity record of Chrons C18n (middle Eocene)-C34n (Late Cretaceous).