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Background: Clostridioides difficile is the most common cause of healthcare-associated diarrhea. Research suggests that treating C. difficile infections (CDI) with fidaxomicin (FDX) is more effective than vancomycin (VAN), with potential cost savings. The objective was to calculate the budget impact of FDX treatment compared to VAN from a German payer perspective., Research Design and Methods: The analysis used real-world data of patients discharged from University Hospital Cologne between Jan-01-2018 and Dec-31-2019. We identified recurrent and non-recurrent CDI cases and calculated direct treatment costs based on G-DRG flat rates. To calculate average costs per treatment and the budget impact, recurrence probabilities for VAN and FDX were taken from published evidence (28-day and 90-day scenarios)., Results: Totally, 475 cases were analyzed, thereof 421 non-recurrent, causing mean costs of €32,901 per case (95% CI: 27.752-38.050). Thirty-two patients experienced a recurrence within 28 days, yielding mean costs of €10,952 (95% CI: 5.627-16.277) for their additional hospital stay. The resulting budget impact was €1,303 (95% CI: 670-1.937) in favor of FDX, ranging from €148.34 to €2,190.30 in scenario analyses., Conclusion: The analysis indicates FDX treatment can lead to cost savings compared to VAN. Future research should focus on specific patient groups, such as refractory CDI patients.

Background: Surgical site infections (SSIs), mainly caused by Staphylococcus aureus, pose a significant economic burden in Europe, leading to increased hospitalization duration, mortality, and treatment costs, particularly with drug-resistant strains such as meticillin-resistant S. aureus., Aim: To conduct a case-control study on the economic impact of S. aureus SSI in adult surgical patients across high-volume centres in France, Germany, Spain, and the UK, aiming to assess the overall and procedure-specific burden across Europe., Methods: The SALT study is a multinational, retrospective cohort study with a nested case-control analysis focused on S. aureus SSI in Europe. The study included participants from France, Germany, Italy, Spain, and the UK who underwent invasive surgery in 2016 and employed a micro-costing approach to evaluate health economic factors, matching S. aureus SSI cases with controls., Findings: In 2016, among 178,904 surgical patients in five European countries, 764 developed S. aureus SSI. Matching 744 cases to controls, the study revealed that S. aureus SSI cases incurred higher immediate hospitalization costs (€8,810), compared to controls (€6,032). Additionally, S. aureus SSI cases exhibited increased costs for readmissions within the first year post surgery (€7,961.6 versus €5,298.6), with significant differences observed. Factors associated with increased surgery-related costs included the cost of hospitalization immediately after surgery, first intensive care unit (ICU) admission within 12 months, and hospital readmission within 12 months, as identified through multivariable analysis., Conclusion: The higher rates of hospitalization, ICU admissions, and readmissions among S. aureus SSI cases highlight the severity of these infections and their impact on healthcare costs, emphasizing the potential benefits of evidence-based infection control measures and improved patient care to mitigate the economic burden., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe., Methods: This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case-control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching., Results: A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure., Conclusions: This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections. Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: Client-therapist physiological synchrony has recently attracted significant empirical attention. Recent theoretical accounts propose that physiological linkages should not be considered a stable dyadic virtue but rather a dynamic process that depends on the situational context in which they transpire. The present study adopted a "momentary" (vs. "global") approach that focuses on therapist-client physiological synchrony over relatively short periods of time. These temporal data served to examine the interplay between patterns of synchrony (in-phase vs. antiphase) and clients' momentary emotional experiences (inhibited/unproductive, productive, and positive). Synchrony was assessed by measuring respiratory sinus arrhythmia (RSA), an autonomic index that is known to be associated with interpersonal emotion regulation., Method: Data were drawn from 28 clients undergoing a 16-session supportive-expressive dynamic therapy for depression. Clients' and therapists' electrocardiography were recorded in five sessions; clients' emotional experiences were coded at the speech-turn level. After each session, the clients also completed the session evaluation scale., Results: Client-therapist dyads had greater momentary RSA synchrony than would be predicted by chance. Compared to moments of unproductive emotional experience, greater antiphase synchrony was observed during moments of productive emotional experiences. In addition, compared to moments of unproductive emotional experience, greater in-phase and antiphase synchrony were observed during moments of positive emotional experiences. These patterns of synchrony were associated with clients' favorable evaluations of the session., Conclusion: By considering the dynamic nature of synchrony, these findings provide a fine-grained picture of physiological synchrony and its potential effects on therapy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Background: The treatment of acute bacterial skin and skin structure infections (ABSSSI) usually involves intravenous (i.v.) antibiotics requiring hospitalisation and increasing hospital costs. Since 2014, dalbavancin is approved for ABSSSIs treatment. However, evidence of its health economic impact on the German healthcare system is still limited., Methods: Diagnosis-related groups (DRG) based cost analysis was used to evaluate real-world data (RWD) from a German tertiary care center. All patients treated with i.v. antibiotics in the Department of Dermatology and Venereology at the University Hospital of Cologne were included to detect potential cost savings from a payer perspective. Thus, for the inpatient care German diagnosis-related groups (G-DRG) tariffs, length of stay (LOS), main- and secondary DRG-diagnoses and for the outpatient setting 'Einheitlicher Bewertungsmaßstab' (EBM) codes were evaluated., Results: This retrospective study identified 480 inpatient cases treated for ABSSSI between January 2016 until December 2020. Complete cost data were available for 433 cases and the detection of long-hospital-stay patients based on surcharges for exceeding the upper limit LOS led to 125 cases (29%) including 67 females (54%) and 58 males (46%) with an overall mean age of 63.6 years; all treated for International Classification of Diseases (ICD -10th revision) code A46 'erysipelas'. A sub-analysis focussed on DRG J64B with a total of 92 cases exceeding the upper limit LOS by a median of 3 days resulted in a median surcharge of €636 (mean value €749; SD €589; IQR €459-€785) per case. In comparison, we calculated outpatient treatment costs of approximately €55 per case. Thus, further treatment of these patients in an outpatient setting before exceeding the upper limit LOS might result in a cost-saving potential of approximately €581 per case., Conclusion: Dalbavancin appears a cost-efficient option to reduce inpatient treatment costs by transitioning to an outpatient setting of patients with ABSSSI potentially exceeding the upper limit LOS., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Die forensische Therapie gemäß §64 StGB zeichnet sich aktuell durch hohe Abbruch- bzw. Erledigungsquoten aus. Das hier vorgestellte verkürzte Therapiekonzept der Klinik für Forensische Psychiatrie des Pfalzklinikums für Patienten mit günstigen Prognosemerkmalen soll durch Förderung von Eigeninitiative, Verantwortung und Motivation sowie eine möglichst individualisierte, störungsorientierte, strafzeit- und tatangemessene Behandlung mit intensiver Erprobung unter Alltagsbedingungen zu einer Verkürzung der stationären Unterbringung führen. Empirische Belege hierfür fehlen jedoch bislang. Erstmals werden hier Pilotdaten aus dem Zeitraum April 2016 bis Mai 2021 vorgestellt. Zusammenfassend hat sich das o.g. Konzept als umsetzbar erwiesen. Die erhobenen Daten weisen darauf hin, dass die im verkürzten Therapieprogramm behandelten Patienten eine geringere Erledigungsquote als der Durchschnitt aller gemäß §64 StGB untergebrachter Patienten aufweist. Eine deutliche Verkürzung der durchschnittlichen Behandlungsdauer ließ sich demgegenüber jedoch nicht belegen. Die vorliegende Arbeit will einen ersten Beitrag zur Diskussion und Weiterentwicklung derartiger Behandlungsoptionen leisten. Mögliche Nachteile derartiger Therapieangebote bei für ungeeignet befundenen Patienten, z. B. eine Abnahme der Therapiemotivation, werden diskutiert.Forensic therapy according to section 64 of the German penal code is currently characterized by high drop-out rates. The shortened therapy concept of the Department of Forensic Psychiatry of the Pfalzklinikum focusing on patients with favorable prognostic characteristics presented here is intended to lead to a shortening of hospital stay by promoting initiative, responsibility and motivation. It is supposed to provide a treatment as individualized and disorder-oriented as possible and appropriate to the individual time of detention as well as the specific kind of offense with intensified testing under everyday conditions. However, so far empirical evidence for this concept is lacking. For the first time, pilot data for the period from April 2016 to May 2021 are presented here. The concept described herein has proven to be feasible. The collected data hint at a lower drop-out rate of patients treated according the shortened therapy concept compared to the average of all patients assigned to forensic treatment according to section 64 of the German penal code. Yet, there was no evidence for a significant shortening of hospital stay. The present work aims at making a first contribution to the discussion and further development of such treatment options. Possible disadvantages for patients who are found to be unsuitable, e. g. those with a decrease in therapeutic motivation, are discussed., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Introduction: Breast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10-40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device., Materials and Methods: 40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated., Results: The study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins., Conclusion: The present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase-III-trial., Competing Interests: Declaration of competing interest M.P. Lux has received honoraria from AstraZeneca, Daiichi-Sankyo Eisai, Exact Sciences, Gilead, Grünenthal, Lilly, medac, MSD, Novartis, Pfizer, pfm, PharmaMar, Pierre-Fabre, Roche, Samantree and Sysmex for advisory boards, lectures, and travel support. M.F. Sandor received travel expenses by Samantree. Other authors have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Several recent research studies show high performance of blood biomarkers to identify Alzheimer's disease also in the pre-dementia mild cognitive impairment (MCI) stage, but data from the routine clinical care memory clinic setting are needed., Methods: We examined plasma samples of 144 memory clinic patients, including dementia of Alzheimer type (DAT, n = 54), MCI (n = 57), and subjective cognitive decline (SCD, n = 33), who either presented as self-referrals or were referred by general practitioners or neurologists or psychiatrists. The plasma biomarkers, amyloid-beta42 (Aß42), amyloid-beta40 (Aß40), phospho-Tau181 (pTau181), total-tau (tTau), and neurofilament light (NFL), as well as different ratios, were measured using the ultrasensitive single molecule array (Simoa) immunoassay technology. Statistical analysis including Kruskal-Wallis test, linear regression, and receiver operating characteristics analyses was performed., Results: Of the single markers, we observed statistically significant group effects of pTau181 (H(2) = 34.43, p < 0.001) and NFL (H(2) = 27.66, p < 0.001). All individual group comparisons of pTau181 were significant, while the contrast of SCD versus MCI for NFL was not significant. In addition, the ratios of Aß42/Aß40 (H(2) = 7.50, p = 0.02) and pTau181/Aß42 (H(2) = 25.26, p < 0.001) showed significant group effects with significant difference between all groups for pTau181/Aß42 and an SCD versus MCI difference for Aß42/Aß40. PTau181 showed the highest area under the curve of 0.85 for the discrimination of SCD and DAT with a sensitivity of 80% and a specificity of 79% at a cut-off of 12.2 pg/mL. Age influenced Aß42, Aß40, and NFL concentrations., Conclusion: Plasma pTau181 and NFL, as well as the ratios Aß42/Aß40 and pTau181/Aß42, are biomarkers, which can differentiate diagnostic groups in a memory clinic setting outside of research studies., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

State-subsidized programs develop medical data integration centers in Germany. To get infection disease (ID) researchers involved in the process of data sharing, common interests and minimum data requirements were prioritized. In 06/2019 we have initiated the German Infectious Disease Data Exchange (iDEx) project. We have developed and performed an online survey to determine prioritization of requests for data integration and exchange in ID research. The survey was designed with three sub-surveys, including a ranking of 15 data categories and 184 specific data items and a query of available 51 data collecting systems. A total of 84 researchers from 17 fields of ID research participated in the survey (predominant research fields: gastrointestinal infections n=11, healthcare-associated and antibiotic-resistant infections n=10, hepatitis n=10). 48% (40/84) of participants had experience as medical doctor. The three top ranked data categories were microbiology and parasitology, experimental data, and medication (53%, 52%, and 47% of maximal points, respectively). The most relevant data items for these categories were bloodstream infections, availability of biomaterial, and medication (88%, 87%, and 94% of maximal points, respectively). The ranking of requests of data integration and exchange is diverse and depends on the chosen measure. However, there is need to promote discipline-related digitalization and data exchange.

Post-implantation embryogenesis is a highly dynamic process comprising multiple lineage decisions and morphogenetic changes that are inaccessible to deep analysis in vivo. We found that pluripotent mouse embryonic stem cells (mESCs) form aggregates that upon embedding in an extracellular matrix compound induce the formation of highly organized "trunk-like structures" (TLSs) comprising the neural tube and somites. Comparative single-cell RNA sequencing analysis confirmed that this process is highly analogous to mouse development and follows the same stepwise gene-regulatory program. Tbx6 knockout TLSs developed additional neural tubes mirroring the embryonic mutant phenotype, and chemical modulation could induce excess somite formation. TLSs thus reveal an advanced level of self-organization and provide a powerful platform for investigating post-implantation embryogenesis in a dish., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objectives: Candidemia is among the most frequent nosocomial bloodstream infections. Landmark case-control studies on amphotericin B and fluconazole estimated attributable mortality rates of 38% and 49%, respectively. After introduction of echinocandins, these may have decreased., Methods: In a case-control design, 100 consecutive, hospitalised patients with candidemia were enrolled at the University Hospital of Cologne, Germany between 2014 and 2017. Controls were patients without candidemia matched for age, sex, year and duration of hospitalisation, main admission diagnosis and Patient Clinical Complexity Level (PCCL). Main data captured were risk factors for candidemia, attributable mortality rates and diagnostic and therapeutic adherence according to the EQUAL Candida score., Results: Overall mortality rates for cases and controls were 43% and 17% (P < .001), respectively; day 30 mortality rates were 38% and 11% (P = .03), accounting for an attributable mortality of 26% and 27%. Guideline adherence was higher in surviving vs non-surviving patients: while survivors reached a median of 17 (IQR: 16-19) points, non-surviving cases reached a median 16 (IQR: 14-18) points out of 22 maximum achievable points (P = .028). Risk factors for candidemia were more frequent in cases compared to control patients, especially chronic pulmonary disease (25% vs 16%; P = n.s.), chronic liver disease (21% vs 6%; P = .002), stay on intensive care unit (70% vs 64%; P = n.s.), respiratory failure (56% vs 50%; P = n.s.) and central venous catheter (97% vs 35%; P < .001)., Conclusions: Attributable mortality of nosocomial candidemia is still substantial but has decreased compared to previous studies with similar design., (© 2020 Wiley-VCH GmbH.)

Purpose: To investigate retinal venous pressure (RVP) as a function of airway pressure (AirP) during the Valsalva maneuver (VM) in human subjects., Methods: Forty-three healthy volunteers (age, 22.0 (2.3) years) (median and interquartile range) were investigated using the following instruments: dynamic contour tonometer, contact lens dynamometer (CLD), and aneroid manometer. The following measurements were performed in their left eyes: tonometry and dynamometry during VM at different levels of airway pressure (AirP = 0, 10, 20, 30, and 40 mmHg)., Results: The median RVP during spontaneous breathing (AirP = 0) was 19.7 (6.4) (median in mmHg (interquartile range)) and the intraocular pressure (IOP) in mydriasis was 16.3 (3.1) mmHg. Spontaneous pulsation occurred in 58.1% of the subjects. RVP increased nonlinearly. The coefficient of variation of four individual measurements of RVP at each pressure level averaged 8.1 (7.6) %. At different AirP levels of 10, 20, 30, and 40 mmHg, the following RVPs were measured: 29.6 (12.6); 34.2 (12.8); 38.0 (10.5); and 40.3 (11.0), respectively. The rise of RVP (Δ RVP) during VM was significantly higher than that of Δ IOP (p < 0.0001, Wilcoxon test). Δ RVP between 0 and 40 mmHg AirP was 20.6 mmHg and Δ IOP 1.5 mmHg. The steepest slope of the RVP/AirP curve was observed at the first step from 0 to 10 mmHg of AirP (∆ RVP = 9.9 mmHg)., Conclusion: A nonlinear relationship between RVP and AirP was found during VM. Small rises in AirP increase the RVP and affect retinal circulation.

Background: Patients with haematological diseases are at high risk of developing Clostridioides difficile infection (CDI)., Aim: The study aim was to describe excess length of stay and costs associated with CDI during the hospital stay for induction chemotherapy in the United States (USA)., Methods: A retrospective analysis was conducted utilizing data from US databases of Truven Health Analytics®. Comprehensive hospitalization data of patients with induction chemotherapy due to acute myeloid leukaemia (AML), acute lymphoblastic leukaemia, Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) were analysed. Patients with CDI occurring during the hospital stay were compared to controls through a case-control comparison of the direct treatment costs and length of stay was performed with an exact matching algorithm., Findings: A total of 2611 patients were included between January 2014 and December 2017. NHL (43.5%) and AML (38.4%) were the predominant underlying diseases and 15% of patients received a stem cell transplantation. During the matching, 105 CDI cases (CDI+) were compared with 801 controls (CDI-). On average, hospitalization costs were increased by US$36,113 in CDI+ compared to CDI- patients (P=0.009) and patients with CDI spent on average 8.9 additional days in hospital (P=0.003)., Conclusions: The findings highlight a significant burden associated with CDI in haematological patients undergoing induction chemotherapy in the USA. There is an important need for prevention of CDI in this specific patient population., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Flank instability and sector collapses, which pose major threats, are common on volcanic islands. On 22 Dec 2018, a sector collapse event occurred at Anak Krakatau volcano in the Sunda Strait, triggering a deadly tsunami. Here we use multiparametric ground-based and space-borne data to show that prior to its collapse, the volcano exhibited an elevated state of activity, including precursory thermal anomalies, an increase in the island's surface area, and a gradual seaward motion of its southwestern flank on a dipping décollement. Two minutes after a small earthquake, seismic signals characterize the collapse of the volcano's flank at 13:55 UTC. This sector collapse decapitated the cone-shaped edifice and triggered a tsunami that caused 430 fatalities. We discuss the nature of the precursor processes underpinning the collapse that culminated in a complex hazard cascade with important implications for the early detection of potential flank instability at other volcanoes.

Background: The healthcare burden of Clostridium (Clostridioides) difficile infection (CDI) is high but not fully characterized., Aim: To assess hospitalization costs, length of hospital stay (LOS) and in-hospital mortality attributable to CDI in the USA by analysing nationwide hospital discharge records over the 2012-2016 period., Methods: A retrospective, observational study based on the Truven Health MarketScan Hospital Drug Database was conducted, in which 46,097 inpatient stays with a diagnosis of CDI were analysed. Costs, LOS and in-hospital mortality were studied for patients with either a principal or secondary (comorbidity) diagnosis of CDI, and for patients re-admitted because of CDI. If CDI was a comorbidity, its attributable burden was estimated by coarsened exact matching, comparing 17,273 CDI stays with 84,164 stays in a control group without a CDI diagnosis., Findings: Inpatients for whom CDI was the main reason for hospitalization incurred mean costs of US$10,528 and an average LOS of 5.9 days. For CDI as a comorbidity, the mean additional cost was US$11,938 and the additional LOS was 4.4 days. CDI also increased the in-hospital mortality rate by 4.1%, on average., Conclusion: This study is consistent with previous publications which demonstrated the high economic burden of CDI for healthcare settings and health insurance systems. When recorded as a comorbidity, CDI significantly increased hospital costs and LOS. These results highlight the need for innovative therapeutic approaches in the prevention and treatment of CDI., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Background: Invasive mucormycosis (IM) is a rare invasive fungal infection with a high mortality rate. However, data concerning the clinical and economic burden of IM are scarce., Aim: To evaluate the direct treatment costs and additional expenditures of patients with IM., Methods: A retrospective cost-of-illness analysis of cases with IM extracted from FungiScope - Global Registry for Emerging Fungal Infections, accessible through the epidemiological research platform www.ClinicalSurveys.net, was undertaken. Results of patients with IM were compared with those of matched patients with similar underlying conditions based on the German Diagnosis Related Group (G-DRG) coding., Findings: Out of 46 patients with probable/proven IM, 31 (67%) patients were male and the median age was 53 years (range 11-88 years). Forty-two patients (92%) had haematological diseases as the most common risk factor. Analysis of cost factors identified antifungal treatment due to IM as the primary cost driver [€22,816, 95% confidence interval (CI) €15,036-32,346], with mean overall direct treatment costs of €53,261 (95% CI €39,660-68,825). Compared with matched patients, patients with IM were treated in hospital for 26.5 additional days (standard deviation 31.8 days; P < 0.001), resulting in mean additional costs of €32,991 (95% CI €21,558-46,613; P < 0.001). Probable IM, as well as absence of chemotherapy, surgical measures due to IM, and antifungal prophylaxis were associated with lower overall costs. Nineteen patients (41.3%) died during hospitalization., Conclusion: This study demonstrates the considerable healthcare burden of IM. The choice of antifungal agent for treatment of IM had no impact on overall cost., (Copyright © 2018 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

A commercial granular metallic iron (Fe 0 ) specimen was used to evaluate the suitability of Fe 0 materials for removing aqueous fluoride (F - ) (water defluoridation). Experiments were performed to characterize the defluoridation potential of the tested Fe 0 as influenced by the presence of chloride (Cl - ) and bicarbonate (HCO 3 - ) ions using tap water (H 2 O) as operational reference system. Duplicate column studies were conducted for 120 days (4 months) using an initial F - concentration of 22.5 mg L -1 , columns flow rates were about 17 mL h -1 . Each column contained a reactive layer (11 cm) made up of 100 g of Fe 0 in a 1:1 volumetric Fe 0 :sand mixture. The reactive layer was sandwiched between two layers of the same sand. A pure sand column was used as control system. After the F - removal experiments, the columns were flushed by methylene blue (MB) and Orange II for 21 days. Removal studies revealed (i) no F - removal in the control system, (ii) no F - significant removal on the Cl - system, (iii) limited F - removal in the HCO 3 - system, and (iv) the best F - removal efficiency in tap water (H 2 O). Dye flushing studies confirmed the ion-selective nature of the Fe 0 /H 2 O system and demonstrated the relatively low efficiency of the same for F - removal. The overall results challenge the prevailing perception that water defluoridation using granular Fe 0 is not possible and suggest that effective water defluoridation in Fe 0 packed-beds is pure a site-specific design issue., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Clostridium difficile infection (CDI) is the most important cause of healthcare-associated infectious diarrhea in industrialized countries. We performed a literature review of the overall economic burden of initial and recurrent CDI as well as of the cost-effectiveness of the various treatment strategies applied in these settings. Even though analysis of health economic data is complicated by the limited comparability of results, our review identified several internationally consistent results. Authors from different countries have shown that recurrent CDI disproportionally contributes to the overall economic burden of CDI and therefore offers considerable saving potential. Subsequent cost-effectiveness analyses almost exclusively identified fidaxomicin as the preferred treatment option for initial CDI and fecal microbiota transplant (FMT) for recurrent CDI. Among the various FMT protocols, optimum results were obtained using early colonoscopy-based FMT., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objectives: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections., Methods: A total of 370 cases from 21 countries were evaluated., Results: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L)., Conclusions: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs., (Copyright © 2017. Published by Elsevier Ltd.)

A systematic study on the microwave-assisted thermolysis of the single source precursor (Et 2 Sb) 2 Te (1) in different asymmetric 1-alkyl-3-methylimidazolium- and symmetric 1,3-dialkylimidazolium-based ionic liquids (ILs) reveals the distinctive role of both the anion and the cation in tuning the morphology and microstructure of the resulting Sb 2 Te 3 nanoparticles as evidenced by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and X-ray photoelectron spectroscopy (XPS). A comparison of the electrical and thermal conductivities as well as the Seebeck coefficient of the Sb 2 Te 3 nanoparticles obtained from different ILs reveals the strong influence of the specific IL, from which C 4 mimI was identified as the best solvent, on the thermoelectric properties of as-prepared nanosized Sb 2 Te 3 . This work provides design guidelines for ILs, which allow the synthesis of nanostructured thermoelectrics with improved performances.

Large volcanic eruptions on Earth commonly occur with a collapse of the roof of a crustal magma reservoir, forming a caldera. Only a few such collapses occur per century, and the lack of detailed observations has obscured insight into the mechanical interplay between collapse and eruption. We use multiparameter geophysical and geochemical data to show that the 110-square-kilometer and 65-meter-deep collapse of Bárdarbunga caldera in 2014-2015 was initiated through withdrawal of magma, and lateral migration through a 48-kilometers-long dike, from a 12-kilometers deep reservoir. Interaction between the pressure exerted by the subsiding reservoir roof and the physical properties of the subsurface flow path explain the gradual, near-exponential decline of both collapse rate and the intensity of the 180-day-long eruption., (Copyright © 2016, American Association for the Advancement of Science.)

Background: Cesarean section (CS) is associated with a moderate-high intensity of postoperative pain. We investigate whether continuous local anesthetic/opioid administration using patient controlled epidural anesthesia (PCEA) is superior in controlling pain after CS than epidural (ED) or intrathecal (IT) opioid bolus administration., Methods: One hundred ninety-nine women undergoing elective CS were randomized into 3 groups: PCEA: Combined spinal-epidural anesthesia (CSE) with a PCEA of ropivacaine 0.1% + sufentanil 0.5 μg/mL for 24 hours after CS. ED: CSE with an ED bolus of 3 mg morphine after CS. IT: spinal anesthesia with an IT bolus of 0.1 mg morphine before CS. Primary objectives were pain (VAS/Visual Analogue Scale 0-100) at 9 h, VAS at 1, 2, 6, 24 and 48 hours, side effects and additional analgesic requirements as secondary endpoints., Results: VAS (rest/mobilization) 10(0-23)/40(20-56) at 9 hours for IT was lower (P=0.11/P=0.003) than VAS 20(0-30)/50(30-60) for ED and 20(0-40)/50(30-70) for PCEA (P=0.005/P=0.01). VAS 10(0-29)/40(20-60) at 6 hours for IT was significantly lower than VAS 20(4-40)/50(30-70) for ED (P=0.02/P=0.02). During mobilization at 24/48 hours VAS 40(20-58)/30(20-40) between IT and PCEA with VAS 50(40-70)/40(20-63) differed significantly (P=0.04/P=0.001). With exception of pruritus, which was less in the PCEA group at 9 hours, side effects were similar in all groups. Ibuprofen consumption in the first 24 hours was significantly lower for IT and PCEA compared to ED., Conclusions: PCEA is less effective then IT and ED opioid bolus administration for post cesarean pain relief. IT provides better analgesia than ED or PCEA, as pointed out by lower ibuprofen consumption.

Thermolysis of the single source precursor (Et2Bi)2Te in DIPB at 80 °C yielded phase-pure Bi4Te3 nanoparticles, while mixtures of Bi4Te3 and elemental Bi were formed at higher temperatures. In contrast, cubic Bi2Te particles were obtained by thermal decomposition of Et2BiTeEt in DIPB. Moreover, a dual source approach (hot injection method) using the reaction of Te(SiEt3)2 and Bi(NMe2)3 was applied for the synthesis of different pure Bi-Te phases including Bi2Te, Bi4Te3 and Bi2Te3, which were characterized by PXRD, REM, TEM and EDX. The influence of reaction temperature, precursor molar ratio and thermolysis conditions on the resulting material phase was verified. Moreover, reactions of alternate bismuth precursors such as Bi(NEt2)3, Bi(NMeEt)3 and BiCl3 with Te(SiEt3)2 were investigated.

Triethylchalcogenostiboranes Et3Sb[double bond, length as m-dash]E (E = S , Se ) were synthesized and their solid state structures were determined. The Sb-Se bond length is the shortest ever reported. Short SbE contacts were not observed. According to quantum chemical calculations, the bonding situation in and is best described as a polarized Sb-E single bond.

GeTe octahedra were prepared by reaction of equimolar amounts of GeCl2·dioxane and Te(SiEt3)2 in oleylamine, whereas a slight excess of the Te precursor yielded GeTe octahedra decorated with elemental Te nanowires, which can be removed by washing with TOP. The mechanism of the GeTe formation is strongly influenced by the solvent. The expected elimination of Et3SiCl (dehalosilylation) only occurred in aprotic solvents, whereas Te(SiEt3)2 was found to react with primary and secondary amines with formation of silylamines. Temperature-dependent studies on the reaction in oleylamine showed that crystalline GeTe particles are formed at temperatures higher than 140 °C. XRD, SAED, and HRTEM studies proved the formation of rhombohedral GeTe nanoparticles. These findings were confirmed by a single-crystal and powder X-ray analysis. The rhombohedral structure modification was found, and the structure was solved in the acentric space group R3m.

The primary cause of uterine scars is a previous cesarean. In women with a previous cesarean, the risks of maternal complications are rare and similar after a trial of labor after cesarean (TOLAC) and after an elective repeat cesarean delivery (ERCD), but the risk of uterine rupture is higher with TOLAC (level of evidence [LE]2). Maternal morbidity in women with previous cesareans is higher when TOLAC fails than when it leads to successful vaginal delivery (LE2). Although maternal morbidity increases progressively with the number of ERCD, maternal morbidity of TOLAC decreases with the number of successful previous TOLAC (LE2). The risk-benefit ratio considering the risks of short- and long-term maternal complications is favorable to TOLAC in most cases (LE3). Globally, neonatal complications are rare regardless of the mode of delivery for women with previous cesareans. The risks of fetal, perinatal, and neonatal mortality during TOLAC are low. Nonetheless, these risks are significantly higher than those associated with ERCD (LE2). The risks of mask ventilation, intubation for meconium-stained amniotic fluid, and neonatal sepsis all increase in TOLAC (LE2). The risk of transient respiratory distress increases in ERCD (LE2). To reduce this risk, and except in particular situations, ERCD must not be performed before 39 weeks (grade B). TOLAC is possible for women with a previous cesarean before 37 weeks, with 2 previous cesareans, with a uterine malformation, a low vertical incision or an unknown incision, with a myomectomy, postpartum fever, an interval of less than 6 months between the last cesarean delivery and the conception of the following pregnancy, if the obstetric conditions are favorable (professional consensus). ERCD is recommended in women with a scar in the uterine body (grade B) and a history of 3 or more cesareans (professional consensus). Ultrasound assessment of the risk of uterine rupture in women with uterine scars has not been shown to have any clinical utility and is therefore not recommended during pregnancy to help decide the mode of delivery (professional consensus). Use of X-ray pelvimetry to decide about TOLAC is associated with an increase in the repeat cesarean rate without any reduction in the rate of uterine rupture (LE2). It is unnecessary for deciding mode of delivery and for managing labor during TOLAC (grade C). TOLAC should be encouraged for women with a previous vaginal delivery either before or after the cesarean, a favorable Bishop score or spontaneous labor, and for preterm births (grade C). For women with a fetus with an estimated weight of more than 4500 g, especially in the absence of a previous vaginal delivery and those with supermorbid obesity (BMI>50), ERCD must be planned from the outset (grade C). For all of the other clinical situations envisioned (maternal age>35 years, diabetes, morbid obesity, prolonged pregnancy, breech presentation and twin pregnancy), TOLAC is possible but the available data do not allow specific guidelines about the choice of mode of delivery, in view of the low levels of proof (grade C). The decision about planned mode of delivery must be shared by the patient and her physician and made by the 8th month, taking into account the individual risk factors for TOLAC failure and uterine rupture (professional consensus). TOLAC is the preferred choice for women who do not have several risk factors (professional consensus). The availability onsite of an obstetrician and anesthetist must be pointed out to the patient. If the woman continues to prefer a repeat cesarean after adequate information and time to think about it, her preference should be honored (professional consensus). Labor should be induced in woman with a previous cesarean only for medical indications (professional consensus). Induction of labor increases the risk of uterine rupture, which can be estimated at 1% if oxytocin is used and 2% with vaginal prostaglandins (LE2). Mechanical methods of induction have not been studied sufficiently. Misoprostol appears to increase the risk of uterine rupture strongly (LE4). Based on the information now available, its use is not recommended (professional consensus). Routine use of internal tocodynamometry does not prevent uterine rupture (professional consensus). The increased risk of uterine rupture associated with oxytocin use is dose-dependent (LE3). In the active phase, it is recommended that the total duration of failure to progress should not exceed 3h; at that point, a cesarean should be performed (professional consensus). Epidural analgesia must be encouraged. The simple existence of a uterine scar is not an indication for a routine manual uterine examination after VBAC (grade C)., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Unprecedented noradamantane-type compounds [(R(2,3)Ge)(4)Te(5)] (R(2) = CH(2)CH(2)COOH, R(3) = CH(CH(2)COOH)(2)), containing a Ge-Ge bond, yield from reactions of R(2,3)GeCl(3) with Na(2)Te or Li(2)Te in THF, while reactions with R(1)GeCl(3) (R(1) = CMe(2)CH(2)COMe) afford a double-decker-type cage [(R(3)Ge)(4)Te(6)]; by reaction with hydrazine, the latter reacts to the hydrazone functionalized, monomeric anion [(R(4)Ge)Te(2)](-) (R(4) = CMe(2)CH(2)CNNH(2)Me).

The major features of chronic obstructive pulmonary disease (COPD) comprise a not fully reversible airflow limitation associated with an abnormal inflammatory response, increased mucus production and development of emphysema-like lesions. Animal models that closely mimic these alterations represent an important issue for the investigation of pathophysiological mechanisms. Since most animal models in this area have focused on specific aspects of the disease, we aimed to investigate whether exposure of C57BL/6 mice to nitrogen dioxide (NO2) may cause a more complex phenotype covering several of the characteristics of the human disease. Therefore, mice were exposed to NO2 for 14h each day for up to 25 days. Initial dose response experiments revealed the induction of a significant inflammatory response at a dose of 20 ppm NO2. Mice developed progressive airway inflammation together with a focal inflammation of the lung parenchyma characterized by a predominant influx of neutrophils and macrophages. In addition, goblet cell hyperplasia was detected in the central airways and increased collagen deposition was found in the lung parenchyma. NO2-exposed mice developed emphysema-like lesions as indicated by a significantly increased mean linear intercept as compared to control mice. Finally, the assessment of lung functional parameters revealed the development of progressive airway obstruction over time. In conclusion, our data provide evidence that the inflammatory response to NO2 exposure is associated with increased mucus production, development of airspace enlargement and progressive airway obstruction. Thus, NO2-exposed mice may serve as a model to investigate pathophysiological mechanisms that contribute to the development of human COPD.

Intramuscular (IM) influenza vaccines are only 30-40% effective in preventing clinical illness among the elderly, and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among nursing-home elderly. Twenty-one institutionalized elderly subjects were vaccinated IN with an inactivated novel vaccine, twice, 21 days apart, and with no adverse effects. Twenty-two subjects were vaccinated once with a commercial IM vaccine. Viral strains used in the 1998/9 vaccine (20 microg of each per dose) were A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94. Serum antibodies (IgG and IgM) and nasal IgA were determined by the hemagglutination inhibition (HI) test and enzyme-linked immunosorbent assay (ELISA), respectively. Mucosal antibody response to the three vaccine strains was detected in 47.6-71.4% and 18.1-31.8% of IN and IM immunized subjects, respectively. Serum antibody response to the three antigens tested was detected in 20.0-61.9% and 18.2-72.7% of IN and IM immunized subjects, respectively. Seroconversion was not significantly different after IN or IM vaccination for both A/Sydney and B/Harbin, but higher for A/Beijing following IM vaccination. On study completion, 57.1, 65.0 and 50.0% of IN vaccinees were seroprotected to A/Beijing, A/Sydney and B/Harbin, respectively. Similarly, 68.1, 77.2 and 54.5% were immune after IM vaccination. The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of morbidity and complications in nursing-home elderly., (Copyright 2002 Elsevier Science Ltd.)

Based on the atomic structures of the mitochondrial cytochrome bc(1) complex, it has been proposed that the soluble domain of the [2Fe-2S] Rieske iron-sulfur protein (ISP) must rotate by ca. 60 degrees and translate through an appreciable distance between two binding sites, proximal to cytochrome c(1) and to the lumen-side quinol binding site. Such motional freedom implies that the electron-transfer rate should be affected by the lumenal viscosity. The flash-induced oxidation of cytochrome f, the chloroplast analogue of cytochrome c(1), was found to be inhibited reversibly by increased lumenal viscosity, as was the subsequent reduction of both cytochrome b(6) and cytochrome f. The rates of these three redox reactions correlated inversely with lumenal viscosity over a viscosity range of 1-10 cP. Reduction of cytochrome b(6) and cytochrome f was not concerted. The rate of cytochrome f reduction was observed to be approximately half that of cytochrome b(6) regardless of the actual viscosity, implying that the path length traversed by the ISP in reduction of cytochrome f is twice that of cytochrome b(6). This suggests that upon initiation of electron transfer by a light flash, cytochrome b(6) reduction requires movement of reduced ISP from an initial position predominantly proximal to cytochrome f, apparently favored by the reduced ISP, to the quinol binding site at which the oxidant-induced reduction of cytochrome b(6) is initiated. Subsequent reduction of cytochrome f requires the additional movement of the ISP back to a site proximal to cytochromef. There is no discernible viscosity dependence for cytochrome b(6) reduction under oxidizing conditions, presumably because the oxidized ISP preferentially binds proximal to the quinone binding niche. The dependence of the cytochrome redox reaction on ambient viscosity implies that the tethered diffusional motion of the ISP is part of the rate limitation for charge transfer through the b(6)f complex.

Cytochrome (cyt) b-559 absorbance changes in intact chloroplasts were deconvoluted using a previously described LED-Array-Spectrophotometer (Klughammer et al. (1990), Photosynth Res 25: 317-327). When intact chloroplasts were isolated in the presence of ascorbate, approx. 15% of the total cyt b-559 could be transiently oxidised by 200 μM H2O2 in the dark. This fraction displays low-potential properties, as it can be also oxidised by menadione in the presence of 5 mM ascorbate. Heat pretreatment increased the size of this fraction by a factor of 3-4. Low concentrations of cyanide (in the μM range) prolonged the oxidation time while high concentrations suppressed the oxidation (I50=1.5 mM KCN). The former KCN-effect relates to inhibition of ascorbate dependent H2O2-reduction which is catalysed by ascorbate peroxidase, whereas the latter effect reflects competition between H2O2 and CN(-) for the same binding site at the cytochrome heme. In the light, much lower concentrations of H2O2 were required to obtain oxidation, the amplitude depending on light intensity and on the concentration of the added H2O2, but never exceeding approx. 15% of the total cyt b-559. In the light, but not in the dark, H2O2 also induced the transient oxidation of a cyt f fraction similar in size to the H2O2-oxidisable cyt b-559 fraction. In this case, H2O2 serves as an acceptor of Photosystem I in conjunction with the ascorbate peroxidase detoxification system. Light can also induce oxidation of a 15% cyt b-559 fraction without H2O2-addition, if nitrite is present as electron acceptor and the chloroplasts are depleted of ascorbate. It is concluded that light-induced cyt b-559 oxidation in vivo is likely to be restricted to the H2O2-oxidisable cyt b-559 LP fraction and is normally counteracted by ascorbate.

Transitional residences are of particular importance among the rehabilitative facilities for the mentally ill that had been called for by the Psychiatry Enquete. Their primary objective is to enable clients cope with (relatively) self-reliant living. Along with achievement, or restoration, of working capacity and its consolidation through (part-time) work, emotional growth, self-assertion, and social skills are to be developed. In view of practical implementation of the theoretical concept outlined in the Psychiatry Enquete, and based on their long years of experience in the field, the authors have drafted guidelines for meaningful professional work in a transitional setting, in view of overcoming recurrent initial difficulties and living up to the high goals envisaged. Client selection and careperson qualification are indispensable prerequisites in the sequenced provision of rehabilitative care, directed both at the vocational and leisure domain and the personal growth of the clients.