F. + H. Engel AG: Erfolg mit releasefähiger Standard-Software

Die Firma F. + H. Engel AG ist ein Bieler Familienunternehmen, das an fünf Standorten tätig ist und die Geschäftsbereiche Stahl, Haustechnik und Eisenwaren abdeckt. Seit über 15 Jahren setzt ENGEL für die Unterstützung ihrer Handelsprozesse die Standardsoftware OpaccOne ein. Dabei orientiert sich das Unternehmen an den durch die Software gegebenen Möglichkeiten, um eine möglichst sichere, stabile und langfristig tragfähige Lösung sicher zu stellen. Dank der Releasefähigkeit der gewählten Standard-Business-Software profitierte Engel ohne grössere Umstellungen von deren laufend erweiterten Fähigkeiten in Bezug auf Funktionalität, Technologie, Anpassungs- und Erweiterungsmöglichkeiten. Dadurch konnte sich ENGEL über die Jahre mit dieser Software stetig weiterentwickeln und auch neue Anforderungen abdecken. Problematisch erwies sich die durch die Einführung eines Webshops deutlich höhere Anforderung an Umfang und Qualität der Produktstammdaten für das umfangreiche Sortiment. Der Aufwand für deren Pflege konnte von ENGEL auf die Dauer nicht geleistet werden. Deshalb entschied man sich für eine zweigleisige Strategie, indem für einen Teil des Sortiments auf die Dienstleistungen eines externen Inhaltsanbieters zurückgegriffen wird

Outcome of standard and high-risk patients with acute anterior circulation stroke after stent retriever thrombectomy.

BACKGROUND AND PURPOSE Stent retrievers have become an important tool for the treatment of acute ischemic stroke. The aim of this study was to analyze outcome and complications in a large cohort of patients with stroke treated with the Solitaire stent retriever. The study also included patients who did not meet standard inclusion criteria for endovascular treatment: low or high baseline National Institutes of Health Stroke Scale score, ≥80 years of age, extensive ischemic signs in middle cerebral artery territory, and time from symptom onset to endovascular intervention>8 hours. METHODS Consecutive patients with acute anterior circulation stroke treated with the Solitaire FR were analyzed. Data on characteristics of endovascular interventions, complications, and clinical outcome were collected prospectively. Patients who met standard inclusion criteria were compared with those who did not. RESULTS A total of 227 patients were included. Mean age was 68.2±14.7 years, and median National Institutes of Health Stroke Scale score on admission was 16 (range, 2-36). Reperfusion was successful (thrombolysis in cerebral infarction, 2b-3) in 70.9%. Outcome was favorable (modified Rankin Scale, 0-2) in 57.7% of patients who met standard inclusion criteria and 30.3% of those who did not. The rates for symptomatic intracranial hemorrhage were 3.7% and 13.1%, for death 11.4% and 33.8%, and for symptomatic intraprocedural complications 2.5% and 4.8%, respectively. CONCLUSIONS Patients<80 years of age, without extensive pretreatment ischemic signs, and baseline National Institutes of Health Stroke Scale score≤30 had high rates of favorable outcome and low periprocedural complication rates after Solitaire thrombectomy. Successful reperfusion was also common in patients not fulfilling standard inclusion criteria, but worse clinical outcomes warrant further research with a special focus on optimal patient selection.

Dose Reduction in Standard Head CT: First Results from a New Scanner Using Iterative Reconstruction and a New Detector Type in Comparison with Two Previous Generations of Multi-slice CT

PURPOSE Computed tomography (CT) accounts for more than half of the total radiation exposure from medical procedures, which makes dose reduction in CT an effective means of reducing radiation exposure. We analysed the dose reduction that can be achieved with a new CT scanner [Somatom Edge (E)] that incorporates new developments in hardware (detector) and software (iterative reconstruction). METHODS We compared weighted volume CT dose index (CTDIvol) and dose length product (DLP) values of 25 consecutive patients studied with non-enhanced standard brain CT with the new scanner and with two previous models each, a 64-slice 64-row multi-detector CT (MDCT) scanner with 64 rows (S64) and a 16-slice 16-row MDCT scanner with 16 rows (S16). We analysed signal-to-noise and contrast-to-noise ratios in images from the three scanners and performed a quality rating by three neuroradiologists to analyse whether dose reduction techniques still yield sufficient diagnostic quality. RESULTS CTDIVol of scanner E was 41.5 and 36.4 % less than the values of scanners S16 and S64, respectively; the DLP values were 40 and 38.3 % less. All differences were statistically significant (p < 0.0001). Signal-to-noise and contrast-to-noise ratios were best in S64; these differences also reached statistical significance. Image analysis, however, showed "non-inferiority" of scanner E regarding image quality. CONCLUSIONS The first experience with the new scanner shows that new dose reduction techniques allow for up to 40 % dose reduction while still maintaining image quality at a diagnostically usable level.

POLG DNA testing as an emerging standard of care before instituting valproic acid therapy for pediatric seizure disorders.

PURPOSE: To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures. METHODS: Four patients who developed VPA-induced hepatotoxicity were examined for POLG sequence variations. A subsequent chart review was used to describe clinical course prior to and after VPA dosing. RESULTS: Four patients of multiple different ethnicities, age 3-18 years, developed VPA-induced hepatotoxicity. All were given VPA due to intractable partial seizures. Three of the patients had developed epilepsia partialis continua. The time from VPA exposure to liver failure was between 2 and 3 months. Liver failure was reversible in one patient. Molecular studies revealed homozygous p.R597W or p.A467T mutations in two patients. The other two patients showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S. Clinical findings and POLG mutations were diagnostic of Alpers-Huttenlocher syndrome. CONCLUSION: Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers-Huttenlocher syndrome can precipitate liver failure. Our data support an emerging proposal that POLG gene testing should be considered in any child or adolescent who presents or develops intractable seizures with or without status epilepticus or epilepsia partialis continua, particularly when there is a history of psychomotor regression.

Predictive Margins and Marginal Effects in Stata

Tables of estimated regression coefficients, usually accompanied by additional information such as standard errors, t-statistics, p-values, confidence intervals or significance stars, have long been the preferred way of communicating results from statistical models. In recent years, however, the limits of this form of exposition have been increasingly recognized. For example, interpretation of regression tables can be very challenging in the presence of complications such as interaction effects, categorical variables, or nonlinear functional forms. Furthermore, while these issues might still be manageable in the case of linear regression, interpretational difficulties can be overwhelming in nonlinear models such as logistic regression. To facilitate sensible interpretation of such models it is often necessary to compute additional results such as marginal effects, predictive margins, or contrasts. Moreover, smart graphical displays of results can be very valuable in making complex relations accessible. A number of helpful commands geared at supporting these tasks have been recently introduced in Stata, making elaborate interpretation and communication of regression results possible without much extra effort. Examples of such commands are -margins-, -contrasts-, and -marginsplot-. In my talk, I will discuss the capabilities of these commands and present a range of examples illustrating their use.

Rationale for reading fluconazole MICs at 24 hours rather than 48 hours when testing Candida spp. by the CLSI M27-A2 standard method.

We investigated if CLSI M27-A2 Candida species breakpoints for fluconazole MIC are valid when read at 24 h. Analysis of a data set showed good correlation between 48- and 24-h MICs, as well as similar outcomes and pharmacodynamic efficacy parameters, except for isolates in the susceptible dose-dependent category, such as Candida glabrata.

Estimating the mean and standard deviation of concentration distributions using censored samples

Environmental data sets of pollutant concentrations in air, water, and soil frequently include unquantified sample values reported only as being below the analytical method detection limit. These values, referred to as censored values, should be considered in the estimation of distribution parameters as each represents some value of pollutant concentration between zero and the detection limit. Most of the currently accepted methods for estimating the population parameters of environmental data sets containing censored values rely upon the assumption of an underlying normal (or transformed normal) distribution. This assumption can result in unacceptable levels of error in parameter estimation due to the unbounded left tail of the normal distribution. With the beta distribution, which is bounded by the same range of a distribution of concentrations, $\rm\lbrack0\le x\le1\rbrack,$ parameter estimation errors resulting from improper distribution bounds are avoided. This work developed a method that uses the beta distribution to estimate population parameters from censored environmental data sets and evaluated its performance in comparison to currently accepted methods that rely upon an underlying normal (or transformed normal) distribution. Data sets were generated assuming typical values encountered in environmental pollutant evaluation for mean, standard deviation, and number of variates. For each set of model values, data sets were generated assuming that the data was distributed either normally, lognormally, or according to a beta distribution. For varying levels of censoring, two established methods of parameter estimation, regression on normal ordered statistics, and regression on lognormal ordered statistics, were used to estimate the known mean and standard deviation of each data set. The method developed for this study, employing a beta distribution assumption, was also used to estimate parameters and the relative accuracy of all three methods were compared. For data sets of all three distribution types, and for censoring levels up to 50%, the performance of the new method equaled, if not exceeded, the performance of the two established methods. Because of its robustness in parameter estimation regardless of distribution type or censoring level, the method employing the beta distribution should be considered for full development in estimating parameters for censored environmental data sets. ^

Cost-benefit analysis: The ``gold standard'' re-examined

The dissertation reviews the recommendations of the Panel on Cost Effectiveness in Health and Medicine (Panel) convened by the US Public Health Service in 1993 in four areas: aggregation of costs and benefits, methods of estimating resources used, definition of population impacted and perspective used in cost benefit analysis. Financial data from a clinical trial was used to test whether different approaches in each of the above four areas would change the net benefit resulting from a cost benefit analysis. Differences in aggregation of cost and benefit resulted in the same net benefit, but not the same cost/benefit ratios. Differences in resource use estimation methods, population subgroups definitions and perspectives all produced different net benefits. Difference in perspective resulted in different and often opposing decisions as to whether the proposed intervention from the clinical trial should be implemented. ^

IN.PACT Amphirion paclitaxel eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial

BACKGROUND The effectiveness and durability of endovascular revascularization therapies for chronic critical limb ischemia (CLI) are challenged by the extensive burden of infrapopliteal arterial disease and lesion-related characteristics (e.g., severe calcification, chronic total occlusions), which frequently result in poor clinical outcomes. While infrapopliteal vessel patency directly affects pain relief and wound healing, sustained patency and extravascular care both contribute to the ultimate "patient-centric" outcomes of functional limb preservation, mobility and quality of life (QoL). METHODS/DESIGN IN.PACT DEEP is a 2:1 randomized controlled trial designed to assess the efficacy and safety of infrapopliteal arterial revascularization between the IN.PACT Amphirion™ paclitaxel drug-eluting balloon (IA-DEB) and standard balloon angioplasty (PTA) in patients with Rutherford Class 4-5-6 CLI. DISCUSSION This multicenter trial has enrolled 358 patients at 13 European centers with independent angiographic core lab adjudication of the primary efficacy endpoint of target lesion late luminal loss (LLL) and clinically driven target lesion revascularization (TLR) in major amputation-free surviving patients through 12-months. An independent wound core lab will evaluate all ischemic wounds to assess the extent of healing and time to healing at 1, 6, and 12 months. A QoL questionnaire including a pain scale will assess changes from baseline scores through 12 months. A Clinical Events Committee and Data Safety Monitoring Board will adjudicate the composite primary safety endpoints of all-cause death, major amputation, and clinically driven TLR at 6 months and other trial endpoints and supervise patient safety throughout the study. All patients will be followed for 5 years. A literature review is presented of the current status of endovascular treatment of CLI with drug-eluting balloon and standard PTA. The rationale and design of the IN.PACT DEEP Trial are discussed. IN.PACT DEEP is a milestone, prospective, randomized, robust, independent core lab-adjudicated CLI trial that will evaluate the role of a new infrapopliteal revascularization technology, the IA-DEB, compared to PTA. It will assess the overall impact on infrapopliteal artery patency, limb salvage, wound healing, pain control, QoL, and patient mobility. The 1-year results of the adjudicated co-primary and secondary endpoints will be available in 2014. TRIAL REGISTRATION NCT00941733

Risk of late effects of treatment in children newly diagnosed with standard-risk acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study cohort

BACKGROUND Treatment of patients with paediatric acute lymphoblastic leukaemia has evolved such that the risk of late effects in survivors treated in accordance with contemporary protocols could be different from that noted in those treated decades ago. We aimed to estimate the risk of late effects in children with standard-risk acute lymphoblastic leukaemia treated with contemporary protocols. METHODS We used data from similarly treated members of the Childhood Cancer Survivor Study cohort. The Childhood Cancer Survivor Study is a multicentre, North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. We included cohort members if they were aged 1·0-9·9 years at the time of diagnosis of acute lymphoblastic leukaemia and had received treatment consistent with contemporary standard-risk protocols for acute lymphoblastic leukaemia. We calculated mortality rates and standardised mortality ratios, stratified by sex and survival time, after diagnosis of acute lymphoblastic leukaemia. We calculated standardised incidence ratios and absolute excess risk for subsequent neoplasms with age-specific, sex-specific, and calendar-year-specific rates from the Surveillance, Epidemiology and End Results Program. Outcomes were compared with a sibling cohort and the general US population. FINDINGS We included 556 (13%) of 4329 cohort members treated for acute lymphoblastic leukaemia. Median follow-up of the survivors from 5 years after diagnosis was 18·4 years (range 0·0-33·0). 28 (5%) of 556 participants had died (standardised mortality ratio 3·5, 95% CI 2·3-5·0). 16 (57%) deaths were due to causes other than recurrence of acute lymphoblastic leukaemia. Six (1%) survivors developed a subsequent malignant neoplasm (standardised incidence ratio 2·6, 95% CI 1·0-5·7). 107 participants (95% CI 81-193) in each group would need to be followed-up for 1 year to observe one extra chronic health disorder in the survivor group compared with the sibling group. 415 participants (376-939) in each group would need to be followed-up for 1 year to observe one extra severe, life-threatening, or fatal disorder in the group of survivors. Survivors did not differ from siblings in their educational attainment, rate of marriage, or independent living. INTERPRETATION The prevalence of adverse long-term outcomes in children treated for standard risk acute lymphoblastic leukaemia according to contemporary protocols is low, but regular care from a knowledgeable primary-care practitioner is warranted. FUNDING National Cancer Institute, American Lebanese-Syrian Associated Charities, Swiss Cancer Research.

The COLOSS BEEBOOK Volume II: Standard methods for Apis mellifera pest and pathogen research

n recent years, declines of honey bee populations have received massive media attention worldwide, yet attempts to understand the causes have been hampered by a lack of standardisation of laboratory techniques. Published as a response to this, the COLOSS BEEBOOK is a unique collaborative venture involving 234 bee scientists from 34 countries, who have produced the definitive guide to how to carry out research on honey bees. It is hoped that these volumes will become the standards to be adopted by bee scientists worldwide. Volume II includes approximately 600 separate protocols dealing with the study of the pests and diseases of the honey bee, Apis mellifera. These cover epidemiology and surveying techniques, virus diseases, bacterial diseases such as European and American foulbrood, fungal and microsporidian diseases such as Nosema, mites such as Acarapis, Varroa and Tropilaelaps, and other pests such as the small hive beetle.