Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.
Abstract Aims To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. Methods and results We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was sympto…
A comparison of some simple methods to identify geographical areas with excess incidence of a rare disease such as childhood leukaemia
SUMMARY Six statistics are compared in a simulation study for their ability to identify geographical areas with a known excess incidence of a rare disease. The statistics are the standardized incidence ratio, the empirical Bayes method of Clayton and Kaldor, Poisson probability, a statistic based on the B statistics are compared for the proportion of true high-risk areas identi"ed in the top 1 per cent and 10 per cent of ranked areas. One of the PW statistics performed consistently well under all circumstances, although the results for the BT statistic were marginally better when only the top 1 per cent of ranked areas was considered. The standardized incidence ratio performed consistently …
Ascorbic acid reduces noise-induced nitric oxide production in the guinea pig ear.
Objectives: Noise-induced hearing loss can be caused, among other causes, by increased nitric oxide (NO) production in the inner ear leading to nitroactive stress and cell destruction. Some studies in the literature suggest that the degree of hearing loss (HL) could be reduced in an animal model through ascorbic acid supplementation. To identify the effect of ascorbic acid on tissue-dependent NO content in the inner ear of the guinea pig, we determined the local NO production in the organ of Corti and the lateral wall separately 6 hours after noise exposure. Study Design: Prospective animal study in guinea pigs. Methods: Over a period of 7 days, male guinea pigs were supplied with minimum (…
Recognition of root canal orifices at a distance – a preliminary study of teledentistry
The remote recognition of root canal orifices was tested on 50 images of endodontically accessed teeth acquired with an intra-oral camera. The images were stored on a laptop computer and were presented to 20 observers who marked the visible canal orifices using software which stored the canal locations in standard files. The marked positions were verified on histological slices. In 87% of the cases, the canal locations were marked correctly. Inter-observer reliability depended on the location of the reviewed root canal (kappa = 0.44–0.77). The detection rate was related to the professional experience of the observers. The maximum proportion of accurate detections was found for the observer…
Untersuchungen zur Entdeckung räumlicher Cluster im Kinderkrebsregister Mainz
Im Rahmen des Mainzer Kinderkrebsregisters beschaftigen wir uns mit der Frage, ob die Inzidenzen kindlicher Krebserkrankungen regional besonders hoch oder besonders niedrig sind. Nicht nur regionale Haufungen sind fur das Register von Interesse, sondern, als Hinweis auf systematische Erfassungslucken, auch regional besonders niedrige Inzidenzen. Dies fuhrt auf die Frage, ob die Inzidenzen von Krebserkrankungen bei Kindern raumliche Autokorrelation aufweisen. Ob man auf einer Landkarte Cluster visuell wahrnimmt und ob Tests auf raumliche Autokorrelation Cluster entdecken, hangt auch von der Klasseneinteilung der beobachteten Werte und von den verwendeten Verfahren ab. Wir haben daher mehrere…
The impact of portal vein tumor thrombosis on survival in patients with hepatocellular carcinoma treated with different therapies: A cohort study.
Background Portal vein tumor thrombosis (PVTT) is a frequent complication of hepatocellular carcinoma (HCC), which leads to classification as advanced stage disease (regardless of the degree of PVTT) according to the Barcelona Clinic Liver Cancer Classification. For such patients, systemic therapy is the standard of care. However, in clinical reality, many patients with PVTT undergo different treatments, such as resection, transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), or best supportive care (BSC). Here we examined whether patients benefited from such alternative therapies, according to the extent of PVTT. Methods This analysis included therapy-naïve …
Determinants of homonym and synonym rates of record linkage in disease registration.
AbstractReliable record linkage is an essential component of the quality of population-based disease registration. Quality assessment of disease registries should, therefore, include quantitative approaches to describe the extent of record-linkage errors. The homonym and synonym rates have been proposed for this purpose. The homonym rate quantifies the proportion of distinct patients excluded from registration due to erroneous linkage with other patients. The synonym rate quantifies the proportion of unrecognized duplicate notifications on patients already registered in the registry. This paper provides an algebraic assessment of the determinants of both rates. It is shown how the homonym a…
Influence of cell proportions and proliferation rates on FDG uptake in squamous-cell esophageal carcinoma: a PET study.
We investigated the influence of cell proportions and proliferation activities on tumor maximum standard uptake value (SUV(max)) in patients with squamous-cell esophageal cancer (SCEC).Sixteen (16) patients with untreated SCEC were examined with (18)F-flourodeoxyglucose positron emission tomography (FDG-PET). The tumor SUV(max) were calculated. Tumors were resected by transthoracic esophagectomy. Tissues were stained with hematoxylin and eosin for the measurement of cell proportions and MIB-1 for measurement of proliferation indices (PIs). Tumor SUV and histologic data were related by using multiple linear regression analysis.The mean proportion of tumor cells in the tumor site was 58.1% (+…
Cancer-associated fibroblasts do not respond to combined irradiation and kinase inhibitor treatment
The emergence of radioresistance is a significant issue in the treatment of squamous cell carcinoma. We recently demonstrated that post-radiogenic extracellular signal-regulated kinase (ERK) signaling might decrease radiosensitivity in this cancer type. To further elucidate how tumor-organizing cell types respond to irradiation and ERK pathway inhibition, we analyzed one oral squamous cell carcinoma and one lung cancer cell line (HNSCCUM-02T, A549), fibroblasts (NIH3T3), primary normal and cancer-associated fibroblasts (CAFs) in vitro. Irradiated cells treated with mitogen-activated protein kinase (MAPK) inhibitor U0126 were screened for pERK levels. Post-radiogenic cellular responses were …
Activation of mitogen-activated protein kinase extracellular signal-related kinase in head and neck squamous cell carcinomas after irradiation as part of a rescue mechanism
Background. Irradiation plays a pivotal role in head and neck squamous cell carcinoma (HNSCC) treatment. However, especially recurrent tumors frequently show increased radioresistance. We analyzed irradiation-stimulated mitogen-activated protein kinase (MAPK) signaling pathways to define cellular rescue mechanisms. Methods. Irradiated HNSCC cells were screened for MAPK activation and results were confirmed and refined by functional analyses. Extracellular signal-regulated kinase (ERK) inhibitor U0126 application enabled us to specify postradiogenic cellu- lar responses. Vascular endothelial growth factor (VEGF) levels were analyzed additionally. Results. We observed a pronounced and time-de…
The recipient CYP2D6 allele 4-associated poor metabolizer status correlates with an early fibrosis development after liver transplantation
Summary CYP2D6 is part of the cytochrome P450 system, which catalyzes biotransformation of endogenous substrates and xenobiotics. Approximately 10% of the Caucasian population has two null alleles, resulting in a poor metabolizer (PM) status. Mostly, allele four (CYP2D6*4) is responsible for the PM status, which is suspected to be associated with an accelerated fibrosis progression (FP). The aim of the present study was to analyze the role of the CYP2D6*4 genotype for FP after liver transplantation (LT). Genotypes were determined in liver biopsies (donor) and peripheral blood (recipient) by fluorescence resonance energy transfer. Data were correlated with clinical variables and risk factors…
Quality of life in melanoma patients during adjuvant treatment with pegylated interferon-α2b: patients’ and doctors’ views
Treatment of malignant melanoma with IFN-α has been associated with significant side-effects. The aim of this retrospective monocentric non-randomized study was first to evaluate the impact on quality of life (QOL) in 30 melanoma patients treated with once weekly 2 μg/kg PEG-IFN-α2b for 18 months, and second to examine whether there is a difference in patients' and physicians' perception of QOL. Data on QOL were collected by means of the EORTC QLQ-C30 questionnaire completed by the patient before consultation at baseline and every three months during treatment. A second questionnaire was filled out independently by the physician, based on the consultation and patient file. All data were rou…
Effects of record linkage errors on disease registration
Abstract:Reliable record linkage is a prerequisite for high-quality population-based disease registration. Rapid developments in computer processing have made record linkage both more efficient and more reliable in recent years. At the same time, concerns about confidentiality increasingly hinder record linkage in many disease registries. This paper provides basic algebraic models describing the effects of record linkage errors on monitoring disease incidence. Homonym errors, that is, erroneous linkage of records that pertain to distinct individuals, lead to underestimation of incidence in the registry population. The degree of underestimation strongly depends on the discriminating power of…
Gentamicin alters nitric oxide production in semicircular canals and otolith organs.
Objectives/Hypothesis: Intratympanic application of gentamicin is an important therapeutic option to control vertigo spells in Meniere's disease. Low doses eliminate the function of semicircular canal ampullae (SCCA) and saccule in most patients, although utricular function is maintained in many cases. Local alteration in free radical production might be responsible for these differences. Therefore, the gentamicin-induced nitric oxide (NO) production was determined in an animal model using separate organ cultures of SCCA, saccule, and utricle. Study Design: Prospective pilot study in male guinea pigs. Methods: SCCA, saccule, and utricle of 28 guinea pigs were isolated and incubated separate…
Non-invasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population
AIMS Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of noninvasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality. METHODS AND RESULTS In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N = 12,599) and fingertip peripheral arterial tonometry (N = 11,125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased e…
Open versus endoscopic bone resection of the dorsolateral calcaneal edge: a cadaveric analysis comparing three dimensional CT scans.
Background It has been claimed that endoscopic calcaneoplasty offers some advantages over open techniques in the surgical treatment of Haglund’s deformity due to reduced postoperative complications like stiffness and pain. Bony over-resection places patients at risk of these complications. The resulting question with regard to the quantitative differences of the extent of the bone removed using these two techniques has not yet been answered. The purpose of the study was to determine the resection volume of calcaneal bone for open and endoscopic surgical techniques. Methods 16 feet obtained from body donors were operated on in equal parts using either open surgical or endoscopic techniques, …
Irregularity of the posterior corneal surface after curved interface femtosecond laser-assisted versus microkeratome-assisted descemet stripping automated endothelial keratoplasty.
During donor tissue preparation for Descemet stripping automated endothelial keratoplasty (DSAEK), either microkeratome or femtosecond laser can be used for intrastromal cutting. We compared morphological and functional outcomes after DSAEK using both cutting techniques.In this retrospective study, 22 uneventful DSAEK surgeries were reviewed. Eight donor corneas were prepared for DSAEK using the VisuMax femtosecond laser (Carl Zeiss Meditec AG, Jena, Germany). Fourteen corneas were processed using an Amadeus II microkeratome (Ziemer Ophthalmic Systems AG, Port, Switzerland). The postoperative best spectacle-corrected visual acuity was measured. Furthermore, corneal optical coherence tomogra…
Pseudonyms for Cancer Registries
AbstractIn order to conform to the rigid German legislation on data privacy and security we developed a new concept of data flow and data storage for population-based cancer registries. A special trusted office generates a pseudonym for each case by a cryptographic procedure. This office also handles the notification of cases and communicates with the reporting physicians. It passes pseudonymous records to the registration office for permanent storage. The registration office links the records according to the pseudonyms. Starting from a requirements analysis we show how to construct the pseudonyms; we then show that they meet the requirements. We discuss how the pseudonyms have to be prote…
Estimating completeness in cancer registries--comparing capture-recapture methods in a simulation study.
Completeness of registration is one of the quality indicators usually reported by cancer registries. This allows researchers to assess how useful and representative the data is. Several methods have been suggested to estimate completeness. In this paper a multi-state model for the process of cancer diagnosis and treatment is presented. In principle, every contact with a doctor during diagnosis, treatment, and aftercare can give rise to a cancer registry notification with a certain probability. Therefore the states included in the model are "incident tumour" and "death" but also contacts with doctors such as consultation of a general practitioner or specialised doctor, diagnostic procedures,…
Increased radioresistance via G12S K-Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer
Background Irradiation-induced signaling via the 2 pathways, Raf-MEK-ERK and PI3K-Akt, is known to be closely associated with a limited response to radiotherapy. In the present study we analyzed the relevance of constitutively active K-Ras for postradiogenic pathway stimulation and the option of coordinated inhibition to overcome these rescue mechanisms. Methods We used 2 epithelial tumor cell lines as a model system, one of them harboring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation and inhibitors on the expression of pERK and pAkt was determined by Western blotting. Additionally, clonogenic assays were performed to functionally …
Transpulmonary cardiac output measurement in a rat model of cardiac arrest and CPR: Impact of vascular access
Objective: The present study investigated the impact of the vascular access site for cardiac output (CO) measurement by thermodilution on survival and neurohistopathological injury in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Secondary the influence of the vascular access site on cardiac output measurements was examined. Methods: Rats underwent asphyxial CA and CPR. Thermocouple probes were either placed via the femoral artery into the bifurcation of abdominal aorta/iliac artery (Femoral) or via the carotid artery into the aortic arch (Carotid). CPR was initiated after 9 min CA. Local cerebral blood flow (lCBF) and CO were assessed for 120 min after restora…
Effects of record linkage errors on registry-based follow-up studies
The importance of reliable record linkage for high quality-population-based disease registration is widely recognized. Systematic methodologic work is lacking, however, on the effects of record linkage errors on the use of disease registries for epidemiologic purposes. The present paper provides algebraic models describing the effects of record linkage errors on monitoring survival of registered patients, which is commonly performed by matching registry records against a database of death certificates, and on registry-based incidence follow-up of external cohorts. Homonym errors, that is, erroneous linkage of records that pertain to distinct individuals, lead to underestimation of survival …
Doxycycline reduces nitric oxide production in guinea pig inner ears.
Abstract Objective Gentamicin application is an important therapeutic option to control vertigo spells in Meniere's disease. However, even in the case of low-dose intratympanic application, gentamicin might contribute to a pathological NO-increase leading to cochlear damage and hearing impairment. The study was performed to evaluate the nitric oxide (NO) reducing capacity of doxycycline in the inner ear after NO-induction by gentamicin. Methods In a prospective animal study, a single dose of gentamicin (10 mg/kg body weight) was injected intratympanically into male guinea pigs (n = 48). The auditory brainstem responses (ABRs) were recorded prior to application and 3, 5 and 7 days afterwards…
Increased basic fibroblast growth factor release and proliferation in xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular endothelial growth factor treatment.
Novel strategies of cancer therapy combine irradiation and anti-angiogenic active compounds. However, little is known concerning the undesired cellular and molecular effects caused by this novel treatment concept. We used a mouse squamous cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired effects which compromise the success of this therapeutic combination. SCCs were subcutanously implanted in nude mice. Animals were treated with a fractionated irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before and after treatment, resonance imaging (MRI), …
Hearing results after hypotympanotomy for glomus tympanicum tumors.
We postulate, that glomus tympanicum tumors (GTTs) may be safely removed without interference with the ossicular chain via a hypotympanotomy approach.Prospective, nonrandomized anatomic and clinical study.Tertiary referral center.All 17 patients between 1989 and 2009 with GTTs without involvement of the lumen of the jugular bulb.We used a modified hypotympanotomy approach. Our technique is a modification of the one first published by Shambaugh (1955). Pure-tone audiograms were performed in all patients. Preoperative and postoperative audiograms were modeled in a linear mixed model evaluating hearing threshold for air and bone conduction and air-bone gap at 500, 1,000, 2,000, and 3,000 Hz. I…
Low SPINK5 expression in chronic rhinosinusitis
Objectives/Hypothesis: Chronic rhinosinusitis (CRS) is a multifactorial disease that probably arises as a result of genetic diversity and environmental factors. SPINK5 is a serine protease inhibitor, which is supposed to be an important regulator of epithelial barrier maintenance. The role of SPINK5 polymorphisms and expression in CRS, especially in individuals with aspirin intolerance, is unclear. Study Design: SPINK5 single-nucleotide polymorphisms (SNPs) and SPINK5 expression levels were correlated with CRS without (CRSsNP) and with nasal polyps (CRSwNP), aspirin intolerance, asthma, and allergies. Methods: One hundred four nasal tissue samples, 15 from patients with CRSsNP, 59 from pati…
Four color-measuring devices compared with a spectrophotometric reference system
Abstract Objectives The objective of this study was to compare the L*C*h° color coordinates of dental color-measuring devices with those of a spectrophotometric reference system. Methods The International Commission on Illumination (CIE) L*C*h° color coordinates of ceramic samples, matching the colors of the VITA Linearguide, were recorded using four color-measuring devices (VITA Easyshade (A), VITA Easyshade compact (B), Degudent Shadepilot (C), X-Rite Shadevision (D)) and a spectrophotometric reference system under standardized test conditions. The intraclass correlation coefficients, regression lines with coefficients of determination, and mean deviations of the dental color-measuring de…
Gentamicin increases nitric oxide production and induces hearing loss in guinea pigs.
Objectives/Hypothesis: Gentamicin application is an important therapeutic option for Meniere's disease. However, even if given at intervals, a destruction of the cochlea was often observed in various animal models together with an increased content of nitric oxide (NO) and reactive oxygen species. The present study was undertaken to identify the correlation between hearing threshold alteration and the NO production in the lateral wall and organ of Corti of the guinea pig in response to gentamicin application. Study Design: Prospective animal study in guinea pigs. Methods: A single dose of gentamicin (10 mg/kg body weight) was injected intratympanally into male guinea pigs and the auditory b…
Cancer risk among residents of Rhineland-Palatinate winegrowing communities: a cancer-registry based ecological study
Abstract Aim To investigate the cancer risk among residents of Rhineland-Palatinate winegrowing communities in an ecological study. Methods On the basis of the Rhineland-Palatinate cancer-registry, we calculated age-adjusted incidence rate ratios for communities with a medium area under wine cultivation (>5 to 20 percent) and a large area under wine cultivation (>20 percent) in comparison with communities with a small area under wine cultivation (>0 to 5 percent). In a side analysis, standardized cancer incidence ratios (SIR) were computed separately for winegrowing communities with small, medium and large area under wine cultivation using estimated German incidence rates as refere…
Power of the Wilcoxon–Mann–Whitney test for non‐inferiority in the presence of death‐censored observations
In clinical trials with patients in a critical state, death may preclude measurement of a quantitative endpoint of interest, and even early measurements, for example for intention-to-treat analysis, may not be available. For example, a non-negligible proportion of patients with acute pulmonary embolism will die before 30 day measurements on the efficacy of thrombolysis can be obtained. As excluding such patients may introduce bias, alternative analyses, and corresponding means for sample size calculation are needed. We specifically consider power analysis in a randomized clinical trial setting in which the goal is to demonstrate noninferiority of a new treatment as compared to a reference t…