Evaluation der methodischen Qualität von Leitlinien der medizinischen Versorgung aus dem System der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften in Deutschland (AWMF)

Leitlinien gewinnen als Hilfen zur Qualitätsförderung und für die Umsetzung notwendiger Reformen im Gesundheitswesen zunehmende Bedeutung. Mit der immer größeren Zahl an veröffentlichten Leitlinien verschiedenster Organisationen steigt aber auch die Sorge um ihre Qualität, inhaltliche Unabhängigkeit und damit auch ihrer tatsächlichen Auswirkungen auf die medizinische Versorgung. In Deutschland haben die Mitgliedsgesellschaften der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) Hunderte von Leitlinien erarbeitet. Eine Qualitätsdarlegung erfolgt durch Selbstbeurteilung der Fachgesellschaften nach drei Entwicklungsstufen: S1 -Handlungsempfehlungen von Expertengruppen, S2 -formale, interdisziplinäre Konsensfindung, S3 -evidenz- und konsensbasierte Leitlinie mit Berücksichtigung von Logik des Versorgungsablaufs, erreichbarem Ergebnis für den Patienten und Abwägung alternativ möglicher Vorgehensweisen. Im Rahmen einer deskriptiven Querschnittsstudie wurde die Zuverlässigkeit der Klassifikation und die tatsächliche Kohärenz dieser Leitlinien zu methodischen Standards anhand einer Zufallsstichprobe geprüft. Dabei sollten Problembereiche erfasst und in einem weiteren Schritt die systematische Verbesserung der Leitlinienentwicklung auf der Grundlage eines „Ist-Soll-Vergleichs“ gewährt werden. Eingeschlossen wurden Leitlinien mit Angabe der Entwicklungsstufe, publiziert über die AWMF-Internetseite, erstellt oder aktualisiert vom 01.09.1997 bis 31.08.2002. Die Einschlusskriterien erfüllten 445 Leitlinien S1, 121 Leitlinien S2 und 17 Leitlinien S3. Für den Vergleich der Gruppen ergab sich bei &#61537;=0.05, &#61538;=0,2 und angenommener Differenz von &#61540;=0,3 ein notwendiger Stichprobenumfang von n=35. Die Stichproben S1 und S2 wurden mit Hilfe eines Zufallsgenerators ermittelt, die S3-Leitlinien wurden aufgrund der zu geringen Anzahl vollständig bewertet. Insgesamt wurden 87 Leitlinien anhand der Checkliste „Methodische Qualität von Leitlinien“ des Ärztlichen Zentrums für Qualität in der Medizin (ÄZQ) bewertet. Diese enthält 44 explizit formulierte Fragen (Kriterien), die gruppiert jeweils einen Beurteilungsbereich abbilden: Qualität der Leitlinienentwicklung (21 Fragen), Inhalt und Format der Leitlinie (17 Fragen), Anwendbarkeit (6 Fragen). Zum Vergleich der Gruppen S1-S3 wurde der Kruskall-Wallis-Test verwandt. Die Bewertung der methodischen Qualität der Leitlinien bestätigt die Validität der S1 – S3-Klassifikation im Sinne einer hoch signifikanten Differenz zwischen den Gruppen (&#61539;² (df = 2) =28,36, p < 0,001). Das Ziel der Klassifikation, dem Nutzer auf einen Blick eine Orientierung über den methodischen Hintergrund einer Leitlinie zu ermöglichen, ist damit erreicht. Die formale Bewertung zeigt auch Bereiche mit Optimierungspotenzial. Bezüglich der Leitlinienentwicklung sind dies vor allem die Diskussion möglicher Interessenkonflikte, externe Begutachtung und Pilottestung der Leitlinie in der Praxis sowie Festlegung der Verantwortlichkeit für Fortschreibung/Aktualisierung. Im Bereich Inhalt und Format sind vor allem die Berücksichtigung der Ansichten und Präferenzen der betroffenen Patienten, Nutzenbewertung von diagnostischen und therapeutischen Verfahren unter Einschluss der Lebensqualität als Zielgröße sowie Abwägung von Nutzen, Kosten und Risiko alternativer Vorgehensweisen anzuführen. Das Hauptproblem ist jedoch bei Kriterien der Anwendbarkeit zu sehen: Verbreitung von geeigneten Anwenderversionen und Schulungsinstrumenten (auch für Patienten), Planung der Implementierung unter Berücksichtigung der damit verbundenen Verhaltensänderung und möglicher Hindernisse sowie Definition geeigneter Messgrößen zur Prüfung von Umsetzung und Auswirkungen der Leitlinie. In dieser Hinsicht sollte das Fortbildungsangebot für Leitlinienentwickler zur Vermittlung methodischer Kenntnisse ausgebaut werden mit einer problemorientierten Beratung und Unterstützung.Die Begutachtung ergab aber auch Schwachpunkte des Bewertungsinstruments. So wird zum Beispiel die Durchführungsqualität des Konsensusprozesses, die entscheidenden Einfluss auf die Qualität und Reproduzierbarkeit der Ergebnisse hat, nicht erfragt. In Zukunft wird es auch wichtig sein, inhaltlich die Qualität von Leitlinien zu erfassen. Dazu wäre eine Zusammenfassung der Schlüsselempfehlungen hilfreich, um Vergleiche gegen den bisherigen „Goldstandard“ (Expertenmeinung) und gegen die Ergebnisse einer systematischen Aufarbeitung der Literatur (Evidenz) zu ermöglichen. Diese Aspekte sollten bei einer Aktualisierung der Checkliste berücksichtigt werden

Contribution of anadromous fish to the diet of European catfish in a large river system

Many anadromous fish species, when migrating from the sea to spawn in fresh waters, can potentially be a valuable prey for larger predatory fish, thereby efficiently linking these two ecosystems. Here, we assess the contribution of anadromous fish to the diet of European catfish (Silurus glanis) in a large river system (Garonne, southwestern France) using stable isotope analysis and allis shad (Alosa alosa) as an example of anadromous fish. Allis shad caught in the Garonne had a very distinct marine delta(13)C value, over 8 per thousand higher after lipid extraction compared to the mean delta(13)C value of all other potential freshwater prey fish. The delta(13)C values of European catfish varied considerably between these two extremes and some individuals were clearly specializing on freshwater prey, whereas others specialized on anadromous fish. The mean contribution of anadromous fish to the entire European catfish population was estimated to be between 53% and 65%, depending on the fractionation factor used for delta(13)C

The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast

The detection and amplification of extracellular signals requires the involvement of multiple protein components. In mammalian cells the receptor of activated C kinase (RACK1) is an important scaffolding protein for signal transduction networks. Further, it also performs a critical function in regulating the cell cycle by modulating the G1/S transition. Many eukaryotic cells express RACK1 orthologs, with one example being Cpc2p in the fission yeast Schizosaccharomyces pombe. In contrast to RACK1, Cpc2p has been described to positively regulate, at the ribosomal level, cells entry into M phase. In addition, Cpc2p controls the stress response pathways through an interaction with Msa2p, and sexual development by modulating Ran1p/Pat1p. Here we describe investigations into the role, which Cpc2p performs in controlling the G protein-mediated mating response pathway. Despite structural similarity to Gβ-like subunits, Cpc2p appears not to function at the G protein level. However, upon pheromone stimulation, cells overexpressing Cpc2p display substantial cell morphology defects, disorientation of septum formation and a significantly protracted G1 arrest. Cpc2p has the potential to function at multiple positions within the pheromone response pathway. We provide a mechanistic interpretation of this novel data by linking Cpc2p function, during the mating response, with its previous described interactions with Ran1p/Pat1p. We suggest that overexpressing Cpc2p prolongs the stimulated state of pheromone-induced cells by increasing ste11 gene expression. These data indicate that Cpc2p regulates the pheromone-induced cell cycle arrest in fission yeast by delaying cells entry into S phase

Quantum critical behaviour in the superfluid density of strongly underdoped ultrathin cuprate films

A central issue in the physics of high temperature superconductors is to understand superconductivity within a single copper-oxide layer or bilayer, the fundamental structural unit in the cuprates, and how it is lost with underdoping. As mobile holes are removed from the CuO_2 planes, the transition temperature T_C and superfluid density n_S decrease in a surprisingly correlated fashion in crystals and thick films. We seek to elucidate the intrinsic physics of bilayers in the strongly underdoped regime, near the critical doping level where superconductivity disappears. We report measurements of n_S(T) in films of Y_{1-x}Ca_xBa_2Cu_3O_{7-\delta} as thin as two copper-oxide bilayers with T_C's as low as 3 K. In addition to seeing the two-dimensional (2D) Kosterlitz-Thouless-Berezinski transition at T_C, we observe a remarkable scaling of T_C with n_S(0) that demonstrates that the disappearance of superconductivity with underdoping is due to quantum fluctuations near a T = 0 2D quantum critical point.Comment: 13 pages, 2 figur

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ

Cigarettes and alcohol in relation to colorectal cancer: the Singapore Chinese Health Study

The relations were examined between colorectal cancer and cigarette smoking and alcohol consumption within the Singapore Chinese Health Study, a population-based, prospective cohort of 63 257 middle-aged and older Chinese men and women enrolled between 1993 and 1998, from whom baseline data on cigarette smoking and alcohol consumption were collected through in-person interviews. By 31 December 2004, 845 cohort participants had developed colorectal cancer (516 colon cancer, 329 rectal cancer). Compared with nondrinkers, subjects who drank seven or more alcoholic drinks per week had a statistically significant, 72% increase in risk of colorectal cancer hazard ratio (HR)=1.72; 95% confidence interval (CI)=1.33–2.22). Cigarette smoking was associated with an increased risk of rectal cancer only. Compared with nonsmokers, HRs (95% CIs) for rectal cancer were 1.43 (1.10–1.87) for light smokers and 2.64 (1.77–3.96) for heavy smokers. Our data indicate that cigarette smoking and alcohol use interact in the Chinese population in an additive manner in affecting risk of rectal cancer, thus suggesting that these two exposures may share a common etiologic pathway in rectal carcinogenesis

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques

Search for direct pair production of the top squark in all-hadronic final states in proton-proton collisions at s√=8 TeV with the ATLAS detector

The results of a search for direct pair production of the scalar partner to the top quark using an integrated luminosity of 20.1fb−1 of proton–proton collision data at √s = 8 TeV recorded with the ATLAS detector at the LHC are reported. The top squark is assumed to decay via t˜→tχ˜01 or t˜→ bχ˜±1 →bW(∗)χ˜01 , where χ˜01 (χ˜±1 ) denotes the lightest neutralino (chargino) in supersymmetric models. The search targets a fully-hadronic final state in events with four or more jets and large missing transverse momentum. No significant excess over the Standard Model background prediction is observed, and exclusion limits are reported in terms of the top squark and neutralino masses and as a function of the branching fraction of t˜ → tχ˜01 . For a branching fraction of 100%, top squark masses in the range 270–645 GeV are excluded for χ˜01 masses below 30 GeV. For a branching fraction of 50% to either t˜ → tχ˜01 or t˜ → bχ˜±1 , and assuming the χ˜±1 mass to be twice the χ˜01 mass, top squark masses in the range 250–550 GeV are excluded for χ˜01 masses below 60 GeV