Implementation of chronic illness care in German primary care practices - how do multimorbid older patients view routine care? A cross-sectional study using multilevel hierarchical modeling
Juliana J. Petersen
Michael A. Paulitsch
Steffi Gerlinde Riedel-Heller
Hendrik van den Bussche
- Background: In primary care, patients with multiple chronic conditions are the rule rather than the exception. The Chronic Care Model (CCM) is an evidence-based framework for improving chronic illness care, but little is known about the extent to which it has been implemented in routine primary care. The aim of this study was to describe how multimorbid older patients assess the routine chronic care they receive in primary care practices in Germany, and to explore the extent to which factors at both the practice and patient level determine their views.
Methods: This cross-sectional study used baseline data from an observational cohort study involving 158 general practitioners (GP) and 3189 multimorbid patients. Standardized questionnaires were employed to collect data, and the Patient Assessment of Chronic Illness Care (PACIC) questionnaire used to assess the quality of care received. Multilevel hierarchical modeling was used to identify any existing association between the dependent variable, PACIC, and independent variables at the patient level (socio-economic factors, weighted count of chronic conditions, instrumental activities of daily living, health-related quality of life, graded chronic pain, no. of contacts with GP, existence of a disease management program (DMP) disease, self-efficacy, and social support) and the practice level (age and sex of GP, years in current practice, size and type of practice).
Results: The overall mean PACIC score was 2.4 (SD 0.8), with the mean subscale scores ranging from 2.0 (SD 1.0, subscale goal setting/tailoring) to 3.5 (SD 0.7, delivery system design). At the patient level, higher PACIC scores were associated with a DMP disease, more frequent GP contacts, higher social support, and higher autonomy of past occupation. At the practice level, solo practices were associated with higher PACIC values than other types of practice.
Conclusions: This study shows that from the perspective of multimorbid patients receiving care in German primary care practices, the implementation of structured care and counseling could be improved, particularly by helping patients set specific goals, coordinating care, and arranging follow-up contacts. Studies evaluating chronic care should take into consideration that a patient’s assessment is associated not only with practice-level factors, but also with individual, patient-level factors.
Trial registration: Current Controlled Trials ISRCTN89818205.
Is contrast medium osmolality a causal factor for contrast-induced nephropathy?
Andreas M. Bucher
Carlo N. De Cecco
U. Joseph Schoepf
Felix G. Meinel
Aleksander W. Krazinski
James V. Spearman
Andrew D. McQuiston
Thomas J. Vogl
Richard W. Katzberg
- The exact pathophysiology of contrast-induced nephropathy (CIN) is not fully clarified, yet the osmotic characteristics of contrast media (CM) have been a significant focus in many investigations of CIN. Osmotic effects of CM specific to the kidney include transient decreases in blood flow, filtration fraction, and glomerular filtration rate. Potentially significant secondary effects include an osmotically induced diuresis with a concomitant dehydrating effect. Clinical experiences that have compared the occurrence of CIN between the various classes of CM based on osmolality have suggested a much less than anticipated advantage, if any, with a lower osmolality. Recent animal experiments actually suggest that induction of a mild osmotic diuresis in association with iso-osmolar agents tends to offset potentially deleterious renal effects of high viscosity-mediated intratubular CM stagnation.
Neurokognitives Enhancement und Hirndoping bei Medizinstudenten in Deutschland : eine quantitative und qualitative Erhebung zum Umgang mit Leistungsdruck
- Der Begriff Hirndoping beschreibt die Einnahme von Medikamenten mit dem Ziel der geistigen Leistungssteigerung. Diese Medikamente sind verschreibungspflichtig und bei den Konsumenten medizinisch nicht indiziert, werden also zweckentfremdet. Mittlerweile ist aus dem Thema Hirndoping ein Thema geworden, welches öffentlich diskutiert wird. Zeitung, Presse und sogar die Film- und Fernsehindustrie beschäftigen sich mit diesem Thema. So nimmt unter anderem die gestresste Mutter Lynette aus der US-Serie «Desperate Housewives» die Ritalin-Tablette ihres Sohnes ein, um so den anstrengenden Alltag besser meistern zu können. In dem US-Film «Ohne Limit - Die Droge für Reichtum und Macht» dreht sich alles um eine Droge, welche die Leistungsfähigkeit ins unermessliche steigern kann.
In der aktuellen Presse findet man immer öfter Schlagzeilen wie beispielsweise Folgendes: „Studenten unter Druck: Hirndoping kein Massenphänomen“.
Doch auch die Lebensmittel- und Pharmaindustrie ist beim Thema Leistungssteigerung in der Ideenfindung sehr kreativ. Manche Substanzen „verleihen einem Flügel“ (Red Bull®), andere sind lecker in Schokolade eingepackt (Pocket Coffee®) und wieder andere sollen die Menschen geistig aktiver machen (Gingium®).
Der Großteil der bisherigen Studien zum Thema Hirndoping stammt aus den Vereinigten Staaten von Amerika. Erst seit kurzer Zeit wird auch die Prävalenz von Hirndoping in Deutschland untersucht. Wie viele Schülerinnen und Schüler sowie Studentinnen und Studenten Substanzen zur geistigen Leistungssteigerung einnehmen, wurde teils schon für bestimmte Regionen und bestimmte Fachrichtungen stichprobenartig ermittelt. Bisher liegen allerdings noch keine umfangreichen Daten zur Prävalenz von Hirndoping bei Medizinstudenten vor. Daher untersuchte diese Studie die Einnahme von Leistungssteigernden Substanzen bei Medizinstudenten in Frankfurt am Main.
Sphingosine-1-phosphate modulates dendritic cell function: focus on non-migratory effects in vitro and in vivo
Heinfried Hermann Radeke
- Dendritic cells (DCs) are the cutting edge in innate and adaptive immunity. The major functions of these antigen-presenting cells are the capture, endosomal processing and presentation of antigens, providing them an exclusive ability to provoke adaptive immune responses and to induce and control tolerance. Immature DCs capture and process antigens, migrate towards secondary lymphoid organs where they present antigens to naive T cells in a well-synchronized sequence of procedures referred to as maturation. Indeed, recent research indicated that sphingolipids are modulators of essential steps in DC homeostasis. It has been recognized that sphingolipids not only modulate the development of DC subtypes from precursor cells but also influence functional activities of DCs such as antigen capture, and cytokine profiling. Thus, it is not astonishing that sphingolipids and sphingolipid metabolism play a substantial role in inflammatory diseases that are modulated by DCs. Here we highlight the function of sphingosine 1-phosphate (S1P) on DC homeostasis and the role of S1P and S1P metabolism in inflammatory diseases.
Controlled intramyocardial release of engineered chemokines by biodegradable hydrogels as a treatment approach of myocardial infarction
Birgit K. Kramp
Tilman M. Hackeng
Elisa A. Liehn
Rory R. Koenen
- Myocardial infarction (MI) induces a complex inflammatory immune response, followed by the remodelling of the heart muscle and scar formation. The rapid regeneration of the blood vessel network system by the attraction of hematopoietic stem cells is beneficial for heart function. Despite the important role of chemokines in these processes, their use in clinical practice has so far been limited by their limited availability over a long time-span in vivo. Here, a method is presented to increase physiological availability of chemokines at the site of injury over a defined time-span and simultaneously control their release using biodegradable hydrogels. Two different biodegradable hydrogels were implemented, a fast degradable hydrogel (FDH) for delivering Met-CCL5 over 24 hrs and a slow degradable hydrogel (SDH) for a gradual release of protease-resistant CXCL12 (S4V) over 4 weeks. We demonstrate that the time-controlled release using Met-CCL5-FDH and CXCL12 (S4V)-SDH suppressed initial neutrophil infiltration, promoted neovascularization and reduced apoptosis in the infarcted myocardium. Thus, we were able to significantly preserve the cardiac function after MI. This study demonstrates that time-controlled, biopolymer-mediated delivery of chemokines represents a novel and feasible strategy to support the endogenous reparatory mechanisms after MI and may compliment cell-based therapies.
Enhancement of Intratumoral Chemotherapy with Cisplatin with or without Microwave Ablation and Lipiodol. Future Concept for Local Treatment in Lung Cancer
Thomas J. Vogl
J. Francis Turner
- Novel therapies for lung cancer are being explored nowadays with local therapies being the tip of the arrow. Intratumoral chemotherapy administration and local microwave ablation have been investigated in several studies. It has been previously proposed that lipiodol has the ability to modify the microenvironment matrix. In our current study we investigated this theory in BALBC mice. In total 160 BALBC mice were divided in eight groups: a) control, b) cisplatin, c) microwave, d) microwave and lipiodol, e) cisplatin and lipiodol, f) microwave and cisplatin, g) lipiodol and h) lipiodol, cisplatin and microwave. Lewis lung carcinoma cell lines (106) were injected into the right back leg of each mouse. After the 8th day, when the tumor volume was about 100mm3 the therapy application was initiated, once per week for four weeks. Magnetic resonance imaging was performed for each tumor when a mouse died or when sacrificed if they were still alive by the end of the experiment (8-Canal multifunctional spool; NORAS MRI products, Gmbh, Germany). Imaging and survival revealed efficient tumor apoptosis for the groups b,c,d,e and f. However; severe toxicity was observed in group h and no follow up was available for this group after the second week of therapy administration. Lipiodol in its current form does assist in a more efficient way the distribution of cisplatin, as the microwave apoptotic effect. Future modification of lipiodol might provide a more efficient method of therapy enhancement. Combination of drug and microwave ablation is possible and has an efficient apoptotic effect.
Association of myeloperoxidase with total and cardiovascular mortality in individuals undergoing coronary angiography - the LURIC study
Marcus E. Kleber
Bernhard R. Winkelmann
Bernhard O. Boehm
- Background: The phagocytic enzyme myeloperoxidase (MPO) acts as a front-line defender against microorganisms. However, increased MPO levels have been found to be associated with complex and calcified atherosclerotic lesions and incident cardiovascular disease. Therefore, this study aimed to investigate a predictive role of MPO, a biomarker of inflammation and oxidative stress, for total and cardiovascular mortality in patients referred to coronary angiography.
Methods and results: MPO plasma concentrations along with eight MPO polymorphisms were determined in 3036 participants of the Ludwigshafen Risk and Cardiovascular Health study (median follow-up 7.75 years). MPO concentrations were positively associated with age, diabetes, smoking, markers of systemic inflammation (interleukin-6, fibrinogen, C-reactive protein, serum amyloid A) and vascular damage (vascular cellular adhesion molecule-1 and intercellular adhesion molecule-1) but negatively associated with HDL-cholesterol and apolipoprotein A-I. After adjustment for cardiovascular risk factors MPO concentrations in the highest versus the lowest quartile were associated with a 1.34-fold risk (95% CI: 1.09–1.67) for total mortality. In the adjusted model the hazard ratio for cardiovascular mortality in the highest MPO quartile was 1.42 (95% CI: 1.07–1.88). Five MPO polymorphisms were positively associated with MPO concentrations but not with mortality. Using Mendelian randomization, we did not obtain evidence for a causal association of MPO with either total or cardiovascular mortality.
Conclusions: MPO concentrations but not genetic variants at the MPO locus are independently associated with risk for total and cardiovascular mortality in coronary artery disease patients.
Selective Lentiviral Gene Delivery to CD133-Expressing Human Glioblastoma Stem Cells
N. Sumru Bayin
Aram S. Modrek
Christian J. Buchholz
Moses V. Chao
Dimitris G. Placantonakis
- Glioblastoma multiforme (GBM) is a deadly primary brain malignancy. Glioblastoma stem cells (GSC), which have the ability to self-renew and differentiate into tumor lineages, are believed to cause tumor recurrence due to their resistance to current therapies. A subset of GSCs is marked by cell surface expression of CD133, a glycosylated pentaspan transmembrane protein. The study of CD133-expressing GSCs has been limited by the relative paucity of genetic tools that specifically target them. Here, we present CD133-LV, a lentiviral vector presenting a single chain antibody against CD133 on its envelope, as a vehicle for the selective transduction of CD133-expressing GSCs. We show that CD133-LV selectively transduces CD133+ human GSCs in dose-dependent manner and that transduced cells maintain their stem-like properties. The transduction efficiency of CD133-LV is reduced by an antibody that recognizes the same epitope on CD133 as the viral envelope and by shRNA-mediated knockdown of CD133. Conversely, the rate of transduction by CD133-LV is augmented by overexpression of CD133 in primary human GBM cultures. CD133-LV selectively transduces CD133-expressing cells in intracranial human GBM xenografts in NOD.SCID mice, but spares normal mouse brain tissue, neurons derived from human embryonic stem cells and primary human astrocytes. Our findings indicate that CD133-LV represents a novel tool for the selective genetic manipulation of CD133-expressing GSCs, and can be used to answer important questions about how these cells contribute to tumor biology and therapy resistance.
The Deletion of Several Amino Acid Stretches of Escherichia coli Alpha-Hemolysin (HlyA) Suggests That the Channel-Forming Domain Contains Beta-Strands
- Escherichia coli α-hemolysin (HlyA) is a pore-forming protein of 110 kDa belonging to the family of RTX toxins. A hydrophobic region between the amino acid residues 238 and 410 in the N-terminal half of HlyA has previously been suggested to form hydrophobic and/or amphipathic α-helices and has been shown to be important for hemolytic activity and pore formation in biological and artificial membranes. The structure of the HlyA transmembrane channel is, however, largely unknown. For further investigation of the channel structure, we deleted in HlyA different stretches of amino acids that could form amphipathic β-strands according to secondary structure predictions (residues 71–110, 158–167, 180–203, and 264–286). These deletions resulted in HlyA mutants with strongly reduced hemolytic activity. Lipid bilayer measurements demonstrated that HlyAΔ71–110 and HlyAΔ264–286 formed channels with much smaller single-channel conductance than wildtype HlyA, whereas their channel-forming activity was virtually as high as that of the wildtype toxin. HlyAΔ158–167 and HlyAΔ180–203 were unable to form defined channels in lipid bilayers. Calculations based on the single-channel data indicated that the channels generated by HlyAΔ71–110 and HlyAΔ264–286 had a smaller size (diameter about 1.4 to 1.8 nm) than wildtype HlyA channels (diameter about 2.0 to 2.6 nm), suggesting that in these mutants part of the channel-forming domain was removed. Osmotic protection experiments with erythrocytes confirmed that HlyA, HlyAΔ71–110, and HlyAΔ264–286 form defined transmembrane pores and suggested channel diameters that largely agreed with those estimated from the single-channel data. Taken together, these results suggest that the channel-forming domain of HlyA might contain β-strands, possibly in addition to α-helical structures.
Oleoyl-lysophosphatidylcholine limits endothelial nitric oxide bioavailability by induction of reactive oxygen species
Michael Sze Ka Wong
Wolfgang F. Graier
- Previously we reported modulation of endothelial prostacyclin and interleukin-8 production, cyclooxygenase-2 expression and vasorelaxation by oleoyl- lysophosphatidylcholine (LPC 18:1). In the present study, we examined the impact of this LPC on nitric oxide (NO) bioavailability in vascular endothelial EA.hy926 cells. Basal NO formation in these cells was decreased by LPC 18:1. This was accompanied with a partial disruption of the active endothelial nitric oxide synthase (eNOS)- dimer, leading to eNOS uncoupling and increased formation of reactive oxygen species (ROS). The LPC 18:1-induced ROS formation was attenuated by the superoxide scavenger Tiron, as well as by the pharmacological inhibitors of eNOS, NADPH oxidases, flavin-containing enzymes and superoxide dismutase (SOD). Intracellular ROS-formation was most prominent in mitochondria, less pronounced in cytosol and undetectable in endoplasmic reticulum. Importantly, Tiron completely prevented the LPC 18:1-induced decrease in NO bioavailability in EA.hy926 cells. The importance of the discovered findings for more in vivo like situations was analyzed by organ bath experiments in mouse aortic rings. LPC 18:1 attenuated the acetylcholine-induced, endothelium dependent vasorelaxation and massively decreased NO bioavailability. We conclude that LPC 18:1 induces eNOS uncoupling and unspecific superoxide production. This results in NO scavenging by ROS, a limited endothelial NO bioavailability and impaired vascular function.