Mortality Following Clostridioides difficile Infection in Europe : A Retrospective Multicenter Case-Control Study

We aimed to describe the clinical presentation, treatment, outcome and report on factors associated with mortality over a 90-day period in Clostridioides difficile infection (CDI). Descriptive, univariate, and multivariate regression analyses were performed on data collected in a retrospective case-control study conducted in nine hospitals from seven European countries. A total of 624 patients were included, of which 415 were deceased (cases) and 209 were still alive 90 days after a CDI diagnosis (controls). The most common antibiotics used previously in both groups were β-lactams; previous exposure to fluoroquinolones was significantly (p = 0.0004) greater in deceased patients. Multivariate logistic regression showed that the factors independently related with death during CDI were older age, inadequate CDI therapy, cachexia, malignancy, Charlson Index, long-term care, elevated white blood cell count (WBC), C-reactive protein (CRP), bacteraemia, complications, and cognitive impairment. In addition, older age, higher levels of WBC, neutrophil, CRP or creatinine, the presence of malignancy, cognitive impairment, and complications were strongly correlated with shortening the time from CDI diagnosis to death. CDI prevention should be primarily focused on hospitalised elderly people receiving antibiotics. WBC, neutrophil count, CRP, creatinine, albumin and lactate levels should be tested in every hospitalised patient treated for CDI to assess the risk of a fatal outcome

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5\u201374.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care

Week 48 resistance analyses of the once-daily, single-tablet regimen darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in adults living with HIV-1 from the Phase III Randomized AMBER and EMERALD Trials

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg is being investigated in two Phase III trials, AMBER (NCT02431247; treatment-naive adults) and EMERALD (NCT02269917; treatment-experienced, virologically suppressed adults). Week 48 AMBER and EMERALD resistance analyses are presented. Postbaseline samples for genotyping/phenotyping were analyzed from protocol-defined virologic failures (PDVFs) with viral load (VL) >= 400 copies/mL at failure/later time points. Post hoc analyses were deep sequencing in AMBER, and HIV-1 proviral DNA from baseline samples (VL = 3 thymidine analog-associated mutations (24% not fully susceptible to tenofovir) detected at screening. All achieved VL <50 copies/mL at week 48 or prior discontinuation. D/C/F/TAF has a high genetic barrier to resistance; no darunavir, primary PI, or tenofovir RAMs were observed through 48 weeks in AMBER and EMERALD. Only one postbaseline M184I/V RAM was observed in HIV-1 of an AMBER participant. In EMERALD, baseline archived RAMs to darunavir, emtricitabine, and tenofovir in participants with prior VF did not preclude virologic response

AN ECONOMIC EVALUATION OF A FINANCIAL REPORTING REGULATION: THE CASE OF STATEMENT NO. 52

This dissertation examines the information content of a financial reporting regulation, Statement No. 52 of the Financial Accounting Standards Board, which regulates the way firms must report for their international subsidiaries. If a signal has information content, market agents will react to its announcement, and abnormal price reaction should be observed. Previous research has shown that market agents react to changes in cash flow but not to changes in earnings not accompanied by corresponding changes in cash flow. This study examines, using various methodologies, the price reaction of securities impacted by Statement No. 52. Four announcement dates are investigated to determine if any abnormal reaction occurs: the date when the proposed regulation (exposure draft) was first announced, the date of the announcement of the revised exposure draft, the date of the announcement of the adoption of the regulation, and the date that firms first announced earnings under the use of the regulation. For the first three dates studied, abnormal reaction was only observed on the date of the announcement of the revised exposure draft. The negative reaction observed is explained by an anticipated decrease in cash flow. This would occur due to the change in the proposed regulation which would cause firms to spend additional economic resources to hedge their increased accounting exposure to exchange rate fluctuations. In examining the earnings announcement date, a model is provided which partitions the earnings announcement into two signals: the reported information caused directly by the regulation, and information that would have been provided had the regulation not been adopted. On this date, abnormal performance was observed due to the earnings which would have been announced had the regulation not been implemented. No abnormal reaction was observed due to the announcement of cosmetic changes in earnings caused by the implementation of the regulation. It is suggested that further analysis of financial regulation, such as the one performed in this dissertation, is needed to provide additional information on the impact of regulatory decisions. This could lead to improved decision making by regulatory agencies

Structure and Miocene evolution of the Gdów tectonic “embayment” (Polish Carpathian Foredeep) : a new model based on reinterpreted seismic data

Analysis of previously available stratigraphic data coupled with the re-interpretation of seismic profiles calibrated by boreholes has allowed the construction of a new tectonic model of evolution of the Gdów “embayment” – a tectonic re-entrant located along the Carpathian front east of Kraków (southern Poland). This model shows that the main phase of localized fault-controlled subsidence took place in the Early Badenian and was associated with deposition of the locally overthickened Skawina Formation. Also, deposition of evaporites of the Wieliczka Formation seems to have been tectonically controlled by local basement faulting. Supra-evaporitic siliciclastic deposits have developed as a result of overall north-directed sediment progradation from the eroded Carpathian belt towards the Carpathian Foredeep. During the final stages of development of the Carpathian fold-and-thrust wedge the previously subsiding Gdów “embayment” area was uplifted and basement faults were reactivated either as reverse faults or as low angle thrust faults. Along the leading edge of this inverted structure a triangle zone developed, with backthrusting along the evaporitic level. As a result, overthickened evaporites, formed in local tectonically-controlled depressions within the area of the Gdów “embayment” area have been strongly folded and internally deformed