Nötige und unnötige Behandlungen beim Hämorrhoidalleiden: Der Patient bestimmt mit

Up to one third of the general population suffers from symptoms caused by hemorrhoids. Conservative treatment comes first unless the patient presents with an acute hemorrhoidal prolapse or a thrombosis. A fiber enriched diet is the primary treatment option, recommended in the perioperative period as well as a long-term prophylaxis. A timely limited application of topical ointments or suppositories and/or flavonoids are further treatment options. When symptoms persist interventional procedures for grade I-II hemorrhoids, and surgery for grade III-IV hemorrhoids should be considered. Rubber band ligation is the interventional treatment of choice. A comparable efficacy using sclerosing or infrared therapy has not yet been demonstrated. We therefore do not recommend these treatment options for the cure of hemorrhoids. Self-treatment by anal insertion of bougies is of lowrisk and may be successful, particularly in the setting of an elevated sphincter pressure. Anal dilation, sphincterotomy, cryosurgery, bipolar diathermy, galvanic electrotherapy, and heat therapy should be regarded as obsolete given the poor or missing data reported for these methods. For a long time, the classic excisional hemorrhoidectomy was considered to be the gold standard as far as surgical procedures are concerned. Primary closure (Ferguson) seems to be superior compared to the "open" version (Milligan Morgan) with respect to postoperative pain and wound healing. The more recently proposed stapled hemorrhoidopexy (Longo) is particularly advisable for circular hemorrhoids. Compared to excisional hemorrhoidectomy the Longo-operation is associated with reduced postoperative pain, shorter operation time and hospital stay as well as a faster recovery, with the disadvantage though of a higher recurrence rate. Data from Hemorrhoidal Artery Ligation (HAL)-, if appropriate in combination with a Recto-Anal Repair (HAL/RAR)-, demonstrates a similar trend towards a better tolerance of the procedure at the expense of a higher recurrence rate. These relatively "new" procedures equally qualify for the treatment of grade III and IV hemorrhoids, and, in the case of stapled hemorrhoidopexy, may even be employed in the emergency situation of an acute anal prolapse. While under certain circumstances different treatment options are equivalent, there is a clear specificity with respect to the application of those procedures in other situations. The respective pros and cons need to be discussed separately with every patient. According to their own requirements a treatment strategy has to be defined according to their individual requirements.

Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection.

BACKGROUND Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10% to 20% during the initial infection and this increases substantially with the need for mechanical ventilation. It has been suggested that corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality in these patients. OBJECTIVES To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxaemia (arterial oxygen partial pressure < 70 mmHg or alveolar-arterial gradient > 35 mmHg on room air). SEARCH METHODS For the original review we searched The Cochrane Library (2004, Issue 4), MEDLINE (January 1980 to December 2004) and EMBASE (January 1985 to December 2004) without language restrictions. We further reviewed the reference lists from previously published overviews, searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts in the field and searched the reference lists of identified publications for citations of additional relevant articles.In this update of our review, we searched the above-mentioned databases in September 2010 and April 2014 for trials published since our original review. We also searched for ongoing trials in ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (ICTRP). We searched for conference abstracts via AEGIS. SELECTION CRITERIA Randomised controlled trials that compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, and reported mortality data. We excluded trials in patients with no or mild hypoxaemia (arterial oxygen partial pressure > 70 mmHg or an alveolar-arterial gradient < 35 mmHg on room air) and trials with a follow-up of less than 30 days. DATA COLLECTION AND ANALYSIS Two teams of review authors independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups using a random-effects model.In this update of our review, we used the GRADE methodology to assess evidence quality. MAIN RESULTS Of 2029 screened records, we included seven studies in the review and six in the meta-analysis. Risk of bias varied: the randomisation and allocation process was often not clearly described, five of seven studies were double-blind and there was almost no missing data. The quality of the evidence for mortality was high. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval (CI) 0.32 to 0.98) at one month and 0.59 (95% CI 0.41 to 0.85) at three to four months of follow-up. In adults, to prevent one death, numbers needed to treat are nine patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. The three largest trials provided moderate quality data on the need for mechanical ventilation, with a risk ratio of 0.38 (95% CI 0.20 to 0.73) in favour of adjunctive corticosteroids. One study was conducted in infants, suggesting a risk ratio for death in hospital of 0.81 (95% CI 0.51 to 1.29; moderate quality evidence). AUTHORS' CONCLUSIONS The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but the evidence from this review suggests a beneficial effect for adult patients with substantial hypoxaemia. There is insufficient evidence on the effect of adjunctive corticosteroids on survival in infants.

Scheduled versus Pro Re Nata Dosing in the VIEW Trials

PURPOSE To analyze visual acuity (VA) outcomes before and after preplanned treatment regimen change in the VIEW studies at week 52 (W52). DESIGN Multiple post hoc analyses for retrospectively defined subgroups in 2 multicenter, multinational, double-masked trials. PARTICIPANTS Two thousand four hundred fifty-seven neovascular age-related macular degeneration (AMD) patients. METHODS Patients were randomized to treatment with 0.5 mg ranibizumab given monthly, a 0.5-mg or 2-mg intravitreal aflibercept injection given monthly, or 2 mg intravitreal aflibercept given every other month, after 3 initial monthly doses, up to W52. From W52 through W96, patients received their original dosing assignment using a capped pro re nata (PRN) regimen, with defined retreatment criteria based on VA and morphologic signs of disease activity and mandatory dosing at least every 12 weeks. MAIN OUTCOME MEASURES Best-corrected VA (BCVA) and optical coherence tomography assessments were mandatory at all visits from baseline to W96. Outcomes were changes in BCVA and central retinal thickness. Outcomes were evaluated in all patients who completed 2 years of the VIEW studies using the last observation carried forward method for missing data at interim visits. RESULTS After W52, approximately 20% of patients lost 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more across all treatment arms with PRN treatment. Patients who met the retreatment criterion of loss of 5 ETDRS letters or more in the first quarter of the PRN dosing phase did not recover; mean final VA loss across the 4 study arms was -4.4 to -5.8 letters. Outcomes of these patients up to W52 were indistinguishable from those of the overall population. There were no differences between groups in serious ocular adverse events or Anti-Platelet Trialists' Collaboration arterial thromboembolic events through W96. CONCLUSIONS These analyses suggest that there are subgroups of patients for whom VA outcomes in the second year of the VIEW studies were less stable than in the first year and for whom W52 seems to be an important inflection point. Although alternate reasons specific to the nature of the underlying AMD cannot be fully excluded, the switch in treatment regimen at W52 is a plausible explanation.

Analysis of Phenotypic Variation in Childhood Wheezing Disorders

Recurrent wheezing or asthma is a common problem in children that has increased considerably in prevalence in the past few decades. The causes and underlying mechanisms are poorly understood and it is thought that a numb er of distinct diseases causing similar symptoms are involved. Due to the lack of a biologically founded classification system, children are classified according to their observed disease related features (symptoms, signs, measurements) into phenotypes. The objectives of this PhD project were a) to develop tools for analysing phenotypic variation of a disease, and b) to examine phenotypic variability of wheezing among children by applying these tools to existing epidemiological data. A combination of graphical methods (multivariate co rrespondence analysis) and statistical models (latent variables models) was used. In a first phase, a model for discrete variability (latent class model) was applied to data on symptoms and measurements from an epidemiological study to identify distinct phenotypes of wheezing. In a second phase, the modelling framework was expanded to include continuous variability (e.g. along a severity gradient) and combinations of discrete and continuo us variability (factor models and factor mixture models). The third phase focused on validating the methods using simulation studies. The main body of this thesis consists of 5 articles (3 published, 1 submitted and 1 to be submitted) including applications, methodological contributions and a review. The main findings and contributions were: 1) The application of a latent class model to epidemiological data (symptoms and physiological measurements) yielded plausible pheno types of wheezing with distinguishing characteristics that have previously been used as phenotype defining characteristics. 2) A method was proposed for including responses to conditional questions (e.g. questions on severity or triggers of wheezing are asked only to children with wheeze) in multivariate modelling.ii 3) A panel of clinicians was set up to agree on a plausible model for wheezing diseases. The model can be used to generate datasets for testing the modelling approach. 4) A critical review of methods for defining and validating phenotypes of wheeze in children was conducted. 5) The simulation studies showed that a parsimonious parameterisation of the models is required to identify the true underlying structure of the data. The developed approach can deal with some challenges of real-life cohort data such as variables of mixed mode (continuous and categorical), missing data and conditional questions. If carefully applied, the approach can be used to identify whether the underlying phenotypic variation is discrete (classes), continuous (factors) or a combination of these. These methods could help improve precision of research into causes and mechanisms and contribute to the development of a new classification of wheezing disorders in children and other diseases which are difficult to classify.

Search for dark matter candidates and large extra dimensions in events with a photon and missing transverse momentum in pp collision data at sqrts=7 TeV w the ATLAS detector

Results of a search for new phenomena in events with an energetic photon and large missing transverse momentum in proton-proton collisions at root s = 7 TeV are reported. Data collected by the ATLAS experiment at the LHC corresponding to an integrated luminosity of 4.6 fb(-1) are used. Good agreement is observed between the data and the standard model predictions. The results are translated into exclusion limits on models with large extra spatial dimensions and on pair production of weakly interacting dark matter candidates.

Search for squarks and gluinos with the ATLAS detector in final states with jets and missing transverse momentum using 4.7 fb⁻¹ of sqrts=7 TeV proton-pro collision data

A search for squarks and gluinos in final states containing jets, missing transverse momentum and no high-p(T) electrons or muons is presented. The data represent the complete sample recorded in 2011 by the ATLAS experiment in 7 TeV proton-proton collisions at the Large Hadron Collider, with a total integrated luminosity of 4.7 fb(-1). No excess above the Standard Model background expectation is observed. Gluino masses below 860 GeV and squark masses below 1320 GeV are excluded at the 95% confidence level in simplified models containing only squarks of the first two generations, a gluino octet and a massless neutralino, for squark or gluino masses below 2 TeV, respectively. Squarks and gluinos with equal masses below 1410 GeV are excluded. In minimal supergravity/constrained minimal supersymmetric Standard Model models with tan beta = 10, A(0) = 0 and mu > 0, squarks and gluinos of equal mass are excluded for masses below 1360 GeV. Constraints are also placed on the parameter space of supersymmetric models with compressed spectra. These limits considerably extend the region of supersymmetric parameter space excluded by previous measurements with the ATLAS detector.

Assessing the Potential of Multiple Imputation in Sequence Analysis

Sequence analysis and optimal matching are useful heuristic tools for the descriptive analysis of heterogeneous individual pathways such as educational careers, job sequences or patterns of family formation. However, to date it remains unclear how to handle the inevitable problems caused by missing values with regard to such analysis. Multiple Imputation (MI) offers a possible solution for this problem but it has not been tested in the context of sequence analysis. Against this background, we contribute to the literature by assessing the potential of MI in the context of sequence analyses using an empirical example. Methodologically, we draw upon the work of Brendan Halpin and extend it to additional types of missing value patterns. Our empirical case is a sequence analysis of panel data with substantial attrition that examines the typical patterns and the persistence of sex segregation in school-to-work transitions in Switzerland. The preliminary results indicate that MI is a valuable methodology for handling missing values due to panel mortality in the context of sequence analysis. MI is especially useful in facilitating a sound interpretation of the resulting sequence types.

Search for supersymmetry in events with large missing transverse momentum, jets, and at least one tau lepton in 20 fb⁻¹ of √s= 8 TeV proton-proton collision data with the ATLAS detector

A search for supersymmetry (SUSY) in events with large missing transverse momentum, jets, at least one hadronically decaying tau lepton and zero or one additional light leptons (electron/muon), has been performed using 20.3 fb−1 of proton-proton collision data at √s = 8TeV recorded with the ATLAS detector at the Large Hadron Collider. No excess above the Standard Model background expectation is observed in the various signal regions and 95% confidence level upper limits on the visible cross section for new phenomena are set. The results of the analysis are interpreted in several SUSY scenarios, significantly extending previous limits obtained in the same final states. In the framework of minimal gauge-mediated SUSY breaking models, values of the SUSY breaking scale ʌ below 63TeV are excluded, independently of tan β. Exclusion limits are also derived for an mSUGRA/CMSSM model, in both the R-parity-conserving and R-parity-violating case. A further interpretation is presented in a framework of natural gauge mediation, in which the gluino is assumed to be the only light coloured sparticle and gluino masses below 1090GeV are excluded.