Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780

The health care setting rather than medical speciality impacts on physicians adherence to guideline-conform anticoagulation in outpatients with non-valvular atrial fibrillation: a cross sectional survey

BACKGROUND: In patients with non-valvular atrial fibrillation (NVAF) at high risk for stroke guidelines consistently recommend long-term oral anticoagulation (OAC) with a vitamin K antagonist. However recommendations remain ambiguous in respect to the precise OAC initiation regimens. Based on the clinical observation, that the initiation of OAC for NVAF varies considerably in daily practice, we aimed to assess the current practice in Switzerland. METHODS: Cross-sectional survey of randomly selected general practitioners, internists and cardiologists from different health care settings in an urban Swiss region that covers 1.4 million inhabitants. The main outcome measures were the preferred antithrombotic initiation regimen and long-term treatment in patients with newly diagnosed NVAF at high risk for stroke. RESULTS: We received 226 out of 388 (58.2%) surveys. Compared to physicians working in a hospital setting (33.6% of respondents) physicians in ambulatory care reported more years of experience and claimed lower-use (never or seldom) of guidelines in general (47.6 vs. 12.2%). Regarding long-term thromboembolic prophylaxis 93.7% of all responders followed current recommendation by choosing an OAC. When focussing on guideline-consistent correct OAC initiation (either low-dose initial OAC or a combination of LMWH and OAC) adherence dropped to 60.6% with hospital physicians demonstrating a significantly higher use of guideline-conform OAC regimens (79.7 vs. 51.0%). Medical speciality in non-hospital physicians was not related to correct guideline-use. Hospital setting remained independently associated with a guideline-conform OAC initiation regimen (OR 2.8, p = 0.023) when controlled for medical speciality, physicians' characteristics and clinical experience. Problems when starting an anticoagulation treatment were seldom reported (never or seldom accounting for 94.1% of all responses). CONCLUSIONS: The guideline adherence with respect to OAC initiation regimens in NVAF was significantly lower when compared to long-term treatment and health care setting rather than medical speciality explained guideline-conform OAC initiation. The majority of the physicians did not consider the initiation of anticoagulation to be a major obstacle in outpatient care

The Short Isoform of the CEACAM1 Receptor in Intestinal T Cells Regulates Mucosal Immunity and Homeostasis via Tfh Cell Induction

Carcinoembryonic antigen cell adhesion molecule like I (CEACAM1) is expressed on activated T cells and signals through either a long (L) cytoplasmic tail containing immune receptor tyrosine based inhibitory motifs, which provide inhibitory function, or a short (S) cytoplasmic tail with an unknown role. Previous studies on peripheral T cells show that CEACAM1-L isoforms predominate with little to no detectable CEACAM1-S isoforms in mouse and human. We show here that this was not the case in tissue resident T cells of intestines and gut associated lymphoid tissues which demonstrated predominant expression of CEACAM1-S isoforms relative to CEACAM1-L isoforms in human and mouse. This tissue resident predominance of CEACAM1-S expression was determined by the intestinal environment where it served a stimulatory function leading to the regulation of T cell subsets associated with generation of secretory IgA immunity, the regulation of mucosal commensalism, and defense of the barrier against enteropathogens

Measurement of inclusive π0\pi^{0} production in hadronic Z0Z^{0} decays

An analysis is presented of inclusive \pi^0 production in Z^0 decays measured with the DELPHI detector. At low energies, \pi^0 decays are reconstructed by \linebreak using pairs of converted photons and combinations of converted photons and photons reconstructed in the barrel electromagnetic calorimeter (HPC). At high energies (up to x_p = 2 \cdot p_{\pi}/\sqrt{s} = 0.75) the excellent granularity of the HPC is exploited to search for two-photon substructures in single showers. The inclusive differential cross section is measured as a function of energy for {q\overline q} and {b \bar b} events. The number of \pi^0's per hadronic Z^0 event is N(\pi^0)/ Z_{had}^0 = 9.2 \pm 0.2 \mbox{(stat)} \pm 1.0 \mbox{(syst)} and for {b \bar b}~events the number of \pi^0's is {\mathrm N(\pi^0)/ b \overline b} = 10.1 \pm 0.4 \mbox{(stat)} \pm 1.1 \mbox{(syst)} . The ratio of the number of \pi^0's in b \overline b events to hadronic Z^0 events is less affected by the systematic errors and is found to be 1.09 \pm 0.05 \pm 0.01. The measured \pi^0 cross sections are compared with the predictions of different parton shower models. For hadronic events, the peak position in the \mathrm \xi_p = \ln(1/x_p) distribution is \xi_p^{\star} = 3.90^{+0.24}_{-0.14}. The average number of \pi^0's from the decay of primary \mathrm B hadrons is found to be {\mathrm N} (B \rightarrow \pi^0 \, X)/\mbox{B hadron} = 2.78 \pm 0.15 \mbox{(stat)} \pm 0.60 \mbox{(syst)}

Search for new phenomena using single photon events in the DELPHI detector at LEP

Data are presented on the reaction \epem~\into~\gamma + no other detected particle at center-of-mass energies, \sqs = 89.48 GeV, 91.26 GeV and 93.08 GeV. The cross section for this reaction is related directly to the number of light neutrino generations which couple to the \zz boson, and to several other phenomena such as excited neutrinos, the production of an invisible `X' particle, a possible magnetic moment of the tau neutrino, and neutral monojets. Based on the observed number of single photon events, the number of light neutrinos which couple to the \zz is measured to be N_\nu = 3.15 \pm 0.34. No evidence is found for anomalous production of energetic single photons, and upper limits at the 95\% confidence level are determined for excited neutrino production (BR < 4-9 \times 10^{-6}), production of an invisible `X' particle (\sigma < 0.1 pb), and the magnetic moment of the tau neutrino (< 5.2 \times 10^{-6} \mu_B). No event with the topology of a neutral monojet is found, and this corresponds to the limit \sigma < 0.044/\epsilon pb at the 95\% confidence level, where \epsilon is the unknown overall monojet detection efficiency

Measurement of the Bd0^{0}_{d} oscillation frequency using kaons, leptons and jet charge

A measurement of the mass difference, \Delta m_d, between the two physical \mbox{B}^0_d states has been obtained from the analysis of the impact parameter distribution of a lepton emitted at large transverse momentum (p_t) relative to the jet axis and from the analysis of the flight distance distribution of secondary vertices tagged by either a high p_t lepton or an identified kaon. In the opposite hemisphere of the event, the charge of the initial quark has been evaluated using a high p_t lepton, a charged kaon or the mean jet charge. With 1.7 million hadronic Z^0 decays recorded by DELPHI between 1991 and 1993, \Delta m_d is found to be: \Delta m_d = 0.531^{+0.050}_{-0.046} ~(stat.) \pm 0.078 ~(syst.) ~ {\mathrm{ps}}^{-1} \,