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International audience; PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13–16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2–0.9) to 0.5 (95% CI, 0.3–1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8–1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

IntroductionPatients with end-stage kidney failure can be treated either by transplant or by dialysis, which can be administered as haemodialysis (HD) or peritoneal dialysis (PD). Although they are equivalent therapeutic options in terms of mortality, the percentage of patients in Germany treated with PD is currently very low (∼6%) compared with other countries. The aim of our study is to analyse the factors behind this percentage and their relevance to the choice of dialysis treatment in Germany. This includes analyses of regional disparities in the provision of care for dialysis patients as well as the evaluations of costs and the influence of reimbursement structures. This approach should provide further insights to explain the variation in the usage of PD and HD and will help to define starting points for future interventions.Methods and analysisA mixed-methods approach will be applied to several data sources, including administrative data (ambulatory physicians’ claim data, statutory health insurance claim data), quality assurance data from one of the largest German dialysis providers Kuratorium für Dialyse (KfH) and qualitative and quantitative survey data (patients, nephrologists and dialysis nurses). Qualitative data will be analysed content-analytically. Based on the quantitative data, multivariable analyses will be performed and, where possible, hierarchical models will be tested. This multidimensional approach will enable us to account for the different factors influencing the penetration of PD in Germany.Ethics and disseminationEthics approval (17-299) has been obtained from the Ethics Committee of the Medical Faculty of the University of Cologne on 25 April 2018. National and international dissemination will be accomplished by informing healthcare practitioners, patients and professional organisations and other stakeholders via conferences, scientific and non-scientific publications and seminars.Trial registration numberDRKS00012555; Pre-Results.

Background The aim of this study was to describe the experience of pediatric and young adult hemodialysis (HD) patients from a global cohort. Methods The Pediatric Investigation and Close Collaborative Consortium for Ongoing Life Outcomes for MONitoring Dialysis Outcomes (PICCOLO MONDO) study provided de-identified electronic information of 3244 patients, ages 0–30 years from 2000 to 2012 in four regions: Asia, Europe, North America and South America. The study sample was categorized into pediatric (≤18 years old) and young adult (19–30 years old) groups based on the age at dialysis initiation. Results For those with known end-stage renal disease etiology, glomerular disease was the most common diagnosis in children and young adults. Using Europe as a reference group, North America [odds ratio (OR) 2.69; CI 1.29, 5.63] and South America (OR 4.21; CI 2.32, 7.63) had the greatest mortality among young adults. North America also had higher rates of overweight, obesity, hypertension, cardiovascular disease, hospitalizations and secondary diabetes compared with all other regions. Initial catheter use was greater for North American (86.4% in pediatric patients and 75.2% in young adults) and South America (80.6% in pediatric patients and 75.9% in young adults). Catheter use at 1-year follow-up was most common in North American children (77.3%) and young adults (62.9%). Asia had the lowest rate of catheter use. For both age groups, dialysis adequacy (equilibrated Kt/V) ranged between 1.4 and 1.5. In Asia, patients in both age groups had significantly longer treatment times than in any other region. Conclusions The PICCOLO MONDO study has provided unique baseline and 1-year follow-up information on children and young adults receiving HD around the globe. This cohort has brought to light aspects of care in these age groups that warrant further investigation.

Background/Aims: Dialysis providers frequently collect detailed longitudinal and standardized patient data, providing valuable registries of routine care. However, even large organizations are restricted to certain regions, limiting their ability to separate effects of local practice from the pathophysiology shared by most dialysis patients. To overcome this limitation, the MONDO (MONitoring Dialysis Outcomes) research consortium has created a platform for the joint analysis of data from almost 200,000 dialysis patients worldwide. Methods: We examined design and operation of MONDO as well as its methodology with respect to patient inclusion, descriptive data and other study parameters. Results: MONDO partners contribute primary databases of anonymized patient data and collaboratively analyze populations across national and regional boundaries. To that end, datasets from different electronic health record systems are converted into a uniform structure. Patients are enrolled without systematic exclusions into open cohorts representing the diversity of patients. A large number of patient level treatment and outcome data is recorded frequently and can be analyzed with little delay. Detailed variable definitions are used to determine if a parameter can be studied in a subset or all databases. Conclusion: MONDO has created a large repository of validated dialysis data, expanding the opportunities for outcome studies in dialysis patients. The density of longitudinal information facilitates in particular trend analysis. Limitations include the paucity of uniform definitions and standards regarding descriptive information (e.g. comorbidities), which limits the identification of patient subsets. Through its global outreach, depth, breadth and size, MONDO advances the observational study of dialysis patients and care.

We classify the complete set of dimension-5 operators relevant for the resonant production of a singlet of spin 0 or 2 linearly coupled to the Standard Model (SM). We compute the decay width of such states as a function of the effective couplings, and provide the matching to various well-motivated New Physics scenarios. We then investigate the possibility that one of these neutral resonances be at the origin of the excess in diboson production recently reported by the ATLAS collaboration. We perform a shape analysis of the excess under full consideration of the systematic uncertainties to extract the width $\Gamma_{\rm tot}$ of the hypothetical resonance, finding it to be in the range 26 GeV $, Comment: 31 pages

We investigate the possibilities of New Physics affecting the Standard Model (SM) Higgs sector. An effective Lagrangian with dimension-six operators is used to capture the effect of New Physics. We carry out a global Bayesian inference analysis, considering the recent LHC data set including all available correlations, as well as results from Tevatron. Trilinear gauge boson couplings and electroweak precision observables are also taken into account. The case of weak bosons tensorial couplings is closely examined and NLO QCD corrections are taken into account in the deviations we predict. We consider two scenarios, one where the coefficients of all the dimension-six operators are essentially unconstrained, and one where a certain subset is loop suppressed. In both scenarios, we find that large deviations from some of the SM Higgs couplings can still be present, assuming New Physics arising at 3 TeV. In particular, we find that a significantly reduced coupling of the Higgs to the top quark is possible and slightly favored by searches on Higgs production in association with top quark pairs. The total width of the Higgs boson is only weakly constrained and can vary between 0.7 and 2.7 times the Standard Model value within 95% Bayesian credible interval (BCI). We also observe sizeable effects induced by New Physics contributions to tensorial couplings. In particular, the Higgs boson decay width into $Z\gamma$ can be enhanced by up to a factor 12 within 95% BCI., Comment: 37 pages, 10 figures, references added, published in JHEP

Reports from a United States cohort of chronic hemodialysis patients suggested that weight loss, a decline in pre-dialysis systolic blood pressure, and decreased serum albumin may precede death. However, no comparative studies have been reported in such patients from other countries. Here we analyzed dynamic changes in these parameters in hemodialysis patients and included 3593 individuals from 5 Asian countries; 35,146 from 18 European countries; 8649 from Argentina; and 4742 from the United States. In surviving prevalent patients, these variables appeared to have notably different dynamics than in patients who died. While in all populations the interdialytic weight gain, systolic blood pressure, and serum albumin levels were stable in surviving patients, these indicators declined starting more than a year ahead in those who died with the dynamics similar irrespective of gender and geographic region. In European patients, C-reactive protein levels were available on a routine basis and indicated that levels of this acute-phase protein were low and stable in surviving patients but rose sharply before death. Thus, relevant fundamental biological processes start many months before death in the majority of chronic hemodialysis patients. Longitudinal monitoring of these dynamics may help to identify patients at risk and aid the development of an alert system to initiate timely interventions to improve outcomes.

We consider the generation of the hierarchical charged lepton spectrum and anarchic neutrino masses and mixing angles in warped extra dimensional models with Randall-Sundrum metric. We have classified all possible cases giving rise to realistic spectra for both Dirac and Majorana neutrinos. An anarchic neutrino spectrum requires a convenient bulk symmetry broken by boundary conditions on both UV and IR branes. We have in particular considered the case of Majorana neutrinos with a continuous bulk symmetry. To avoid unwanted massless extra gauge bosons the 4D group should be empty. If the 4D coset is not vanishing it can provide a Wilson Line description of the neutrino Majorana mass matrix. We have studied an example based on the bulk gauge group U(3)_{L} \otimes U(3)_{N} \otimes_{i} U(1)_{E^i} with the Wilson Line in SO(3)_{N} satisfying all required conditions. A \chi^2-fit to experimental data exhibits the 95% CL region in the parameter space with no fine-tuning. As a consequence of the symmetries of the theory there is no tree-level induced lepton flavor violation and so one-loop processes are consistent with experimental data for KK-modes about a few TeV. The model is easily generalizable to models with IR deformed metrics with similar conclusions., Comment: 28 pages, 9 eps plots, uses axodraw; v2 Title changed, comments on phenomenology added, version to be published in JHEP

Five dimensional warped spaces with soft walls are generalizations of the standard Randall-Sundrum compactifications, where instead of an infrared brane one has a curvature singularity (with vanishing warp factor) at finite proper distance in the bulk. We project the physics near the singularity onto a hypersurface located a small distance away from it in the bulk. This results in a completely equivalent description of the soft wall in terms of an effective infrared brane, hiding any singular point. We perform explicitly this calculation for two classes of soft wall backgrounds used in the literature. The procedure has several advantages. It separates in a clean way the physics of the soft wall from the physics of the five dimensional bulk, facilitating a more direct comparison with standard two-brane warped compactifications. Moreover, consistent soft walls show a sort of universal behavior near the singularity which is reflected in the effective brane Lagrangian. Thirdly, for many purposes, a good approximation is obtained by assuming the bulk background away from the singularity to be the usual Randall-Sundrum metric, thus making the soft wall backgrounds better analytically tractable. We check the validity of this procedure by calculating the spectrum of bulk fields and comparing it to the exact result, finding very good agreement., 14 pages, 2 figures, v2: subsection on IR brane potentials and appendix on fermions added, version to appear in PRD

We employ the covariant background formalism to derive generic expressions for the one-loop effective action in field theoretic orbifold compactifications. The contribution of each orbifold sector is given by the effective action of its fixed torus with a shifted mass matrix. We thus study in detail the computation of the heat kernel on tori. Our formalism manifestly separates UV sensitive (local) from UV-insensitive (nonlocal) renormalization. To exemplify our methods, we study the effective potential of 6d gauge theory as well as kinetic terms for gravitational moduli in 11d supergravity., Comment: 30 pages, 1 figure, 3 tables, v2: appendix on zeta function regularization added, discussion of 6d example expanded, version to appear in JHEP

We analyze the Scherk-Schwarz (SS) supersymmetry breaking in brane-world five dimensional theories compactified on the orbifold $S^1/\mathbb{Z}_2$. The SS breaking parameter is undetermined at the tree-level (no-scale supergravity) and can be interpreted as the Hosotani vacuum expectation value corresponding to the $U(1)_R$ group in five dimensional N=2 (ungauged) supergravity. We show that the SS breaking parameter is fixed at the loop level to either 0 or 1/2 depending on the matter content propagating in the bulk but in a rather model-independent way. Supersymmetry breaking is therefore fixed through a radiative Scherk-Schwarz mechanism. We also show that the two discrete values of the SS parameter, as well as the supersymmetry breaking shift in the spectrum of the bulk fields, are altered in the presence of a brane-localized supersymmetry breaking arising from some hidden sector dynamics. The interplay between the SS and the brane localized breaking is studied in detail., 16 pages, 2 figures, uses axodraw. References added

This is Version nr. 2 (28 Aug 2001) of the original paper (11 Apr 2001). Includes corrected typos., We analyze the one-loop ultraviolet sensitivity of the Higgs mass in a five-dimensional supersymmetric theory compactified on the orbifold S^1/Z_2, with superpotential localized on a fixed-point brane. Four-dimensional supersymmetry is broken by Scherk-Schwarz boundary conditions. Kaluza-Klein interactions are regularized by means of a brane Gaussian distribution along the extra dimension with length l_s\simeq\Lambda^{-1}_s, where \Lambda_s is the cutoff of the five-dimensional theory. The coupling of the n-mode, with mass M^{(n)}, acquires the n-dependent factor exp{-(M^{(n)}/\Lambda_s)^2/2}, which makes it to decouple for M^{(n)}\gg \Lambda_s. The sensitivity of the Higgs mass on \Lambda_s is strongly suppressed and quadratic divergences cancel by supersymmetry. The one-loop correction to the Higgs mass is finite and equals, for large values of \Lambda_s, the value obtained by the so-called KK-regularization., Work supported in part by CICYT, Spain, under contract AEN98-0816, and by EU under contracts HPRN-CT-2000-00152 and HPRN-CT-2000-00148.

We examine trilinear and quartic anomalous gauge couplings (AGCs) generated in composite Higgs models and models with warped extra dimensions. We first revisit the SU(2)_L x U(1)_Y effective Lagrangian and derive the charged and two-photon neutral AGCs. We derive the general perturbative contributions to the pure field-strength operators from spin 0, 1/2, 1 resonances by means of the heat kernel method. In the composite Higgs framework, we derive the pattern of expected deviations from typical SO(N) embeddings of the light composite top partner. We then study a generic warped extra dimension framework with AdS_5 background, recasting in few parameters the features of models relevant for AGCs. We also present a detailed study of the latest bounds from electroweak and Higgs precision observables, with and without brane kinetic terms. For vanishing brane kinetic terms, we find that the S and T parameters exclude KK gauge modes of the RS custodial [non-custodial] scenario below 7.7 [14.7] TeV, for a brane Higgs and below 6.6 [8.1] TeV for a Pseudo Nambu-Goldstone Higgs, at 95% CL. These constraints can be relaxed in presence of brane kinetic terms. The leading AGCs are probing the KK gravitons and the KK modes of bulk gauge fields in parts of the parameter space. In these scenarios, the future CMS and ATLAS forward proton detectors could be sensitive to the effect of KK gravitons in the multi-TeV mass range., Comment: 37 pages, 2 figures, 3 tables. Minor typos fixed, some comments and references added. Matches JHEP version

We consider scenarios of Higgs compositeness where the Higgs doublet arises as a pseudo-Nambu Goldstone boson. Our focus is the physical scalar ("radial") excitation associated with the global symmetry breaking vacuum, which we call the "global Higgs". For the minimal case of a $SO(5)/SO(4)$ coset, the couplings of the global Higgs to Standard Model (SM) particles are fully determined by group theoretical factors and two decay constants. The global Higgs also couples to the composite resonances of the theory, inducing an interaction with the SM gauge bosons at one-loop. We thoroughly analyze representative fermionic sectors, considering a global Higgs both in the $\bf 5$ and $\bf 14$ representations of $SO(5)$ and taking into account the renormalization group evolution of couplings in the composite sector. We derive the one-loop effective couplings and all decays of the global Higgs, showing that its decay width over mass can range from $ O (10^{-3})$ to $ O(1)$. Because of the multiplicity of the resonances, the coupling of the global Higgs to gluons is sizeable, potentially opening a new window into composite models at the LHC., 27 pages, 2 figures. v3: References and comments added. Matches JHEP version