Costs and resource utilization patterns in surgical site infections: a pre-COVID-19 perspective from France, Germany, Spain, and the UK.

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.

Excess burden associated with Clostridioides difficile infection in haematological patients occurring during hospitalization with induction chemotherapy in the USA.

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.

Burden of Clostridium (Clostridioides) difficile infection during inpatient stays in the USA between 2012 and 2016.

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.

Healthcare burden of probable and proven invasive mucormycosis: a multi-centre cost-of-illness analysis of patients treated in tertiary care hospitals between 2003 and 2016.

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.

Induced seismicity response of hydraulic fracturing: results of a multidisciplinary monitoring at the Wysin site, Poland.

Shale oil and gas exploitation by hydraulic fracturing experienced a strong development worldwide over the last years, accompanied by a substantial increase of related induced seismicity, either consequence of fracturing or wastewater injection. In Europe, unconventional hydrocarbon resources remain underdeveloped and their exploitation controversial. In UK, fracturing operations were stopped after the Mw 2.3 Blackpool induced earthquake; in Poland, operations were halted in 2017 due to adverse oil market conditions. One of the last operated well at Wysin, Poland, was monitored independently in the framework of the EU project SHEER, through a multidisciplinary system including seismic, water and air quality monitoring. The hybrid seismic network combines surface mini-arrays, broadband and shallow borehole sensors. This paper summarizes the outcomes of the seismological analysis of these data. Shallow artificial seismic noise sources were detected and located at the wellhead active during the fracturing stages. Local microseismicity was also detected, located and characterised, culminating in two events of Mw 1.0 and 0.5, occurring days after the stimulation in the vicinity of the operational well, but at very shallow depths. A sharp methane peak was detected ~19 hours after the Mw 0.5 event. No correlation was observed between injected volumes, seismicity and groundwater parameters.

Economic burden and cost-effective management of Clostridium difficile infections.

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.

Synthesis, structure and dispersion interactions in bis(1,8-naphthalendiyl)distibine.

Naph2Sb21 was synthesized by a reaction of 1,8-dilithionaphthalene NaphLi2 with SbCl3 and its solid state structure is reported on. 1 shows intermolecular interactions in the solid state, which were studied by quantum chemical calculations with dispersion corrected density functional theory, supermolecular ab initio approaches and symmetry adapted perturbation theory. The same methods were employed to compare the solid state interactions in the crystal of 1 to those in real (for E = P) and hypothetical (for E = As and Bi) crystal structures of Naph2E2. Dispersion interactions were found to provide the most important stabilising contribution in all cases, seconded by electrostatic attraction between pnictogen atoms and π-systems of neighbouring naphthyl groups.

A prospective international Aspergillus terreus survey: an EFISG, ISHAM and ECMM joint study.

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.

Economic burden of Clostridium difficile associated diarrhoea: a cost-of-illness study from a German tertiary care hospital.

PURPOSE: Clostridium difficile associated diarrhoea (CDAD) is the most common cause of health-care-associated infectious diarrhoea. In the context of the German health-care system, direct and indirect costs of an initial episode of CDAD and of CDAD recurrence are currently unknown. METHODS: We defined CDAD as presence of diarrhoea (≥3 unformed stools/day) in association with detection of Clostridium difficile toxin in an unformed faecal sample. Patients treated with metronidazole (PO or IV) and/or vancomycin (PO) were included. Comprehensive data of patients were retrospectively documented into a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). Patients with CDAD were matched to control patients in a 1:1 ratio. Analysis was split in three groups: incidence group (CDAD patients without recurrence), recurrence group (CDAD patients with ≥1 recurrence) and control group (matched non-CDAD patients). RESULTS: Between 02/2010 and 12/2011, 150 patients with CDAD (114 patients in the incidence and 36 (24 %) in the recurrence group) and 150 controls were analysed. Mean length of stay was: 32 (95 %CI: 30-37), 94 (95 %CI: 76-112) and 24 days (95 %CI: 22-27; P = <0.001), resulting in mean overall direct treatment costs per patient of €18,460 (95 %CI: €14,660-€22,270), €73,900 (95 %CI: €50,340-€97,460) and €14,530 (95 %CI: €11,730-€17,330; P = <0.001). In the incidence and recurrence group, the mean cumulative number of antibiotic CDAD treatment days was 11 (95 %CI: 10-12) and 36 (95 %CI: 27-45; P = <0.001). CONCLUSIONS: Especially CDAD recurrence was associated with excessive costs, which were mostly attributable to a significantly longer overall length of stay. Innovative treatment strategies are warranted to reduce treatment costs and prevent recurrence of CDAD.

Candidemia in the intensive care unit: analysis of direct treatment costs and clinical outcome in patients treated with echinocandins or fluconazole.

Direct treatment costs caused by candidemia in German intensive care unit (ICU) patients are currently unknown. We analyzed treatment costs and the impact of antifungal drug choice. Comprehensive data of patients who had at least one episode of candidemia while staying in the ICU between 01/2005 and 12/2010 were documented in a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). A detailed analysis of all disease-associated treatment costs was performed. Patients treated with echinocandins (i.e., anidulafungin, caspofungin, micafungin) or fluconazole were analyzed separately and compared. Forty-one and 64 patients received echinocandins and fluconazole, respectively. The mean Acute Physiology and Chronic Health Evaluation (APACHE) IV score was 114 (95 % confidence interval [CI]: 106-122) vs. 95 (95 % CI: 90-101, p = <0.001). Twenty-three (56 %) and 33 (52 %, p = 0.448) patients survived hospitalization, while 17 (41 %) and 22 (34 %, p = 0.574) survived one year after diagnosis. In the echinocandin and fluconazole groups, the mean costs per patient of ICU treatment were 20,338 (95 % CI: 12,893-27,883) vs. 11,932 (95 % CI: 8,016-15,849, p = 0.110), and the total direct treatment costs per patient were 37,995 (95 % CI: 26,614-49,376) vs. 22,305 (95 % CI: 16,817-27,793, p = 0.012), resulting in daily costs per patient of 1,158 (95 % CI: 1,036-1,280) vs. 927 (95 % CI: 828-1,026, p = 0.001). Our health economic analysis shows the high treatment costs of patients with candidemia in the ICU. Sicker patients had a prolonged hospitalization and were more likely to receive echinocandins, leading to higher treatment costs. Outcomes were comparable to those achieved in less sick patients with fluconazole.

Different doses of micafungin for prophylaxis of invasive fungal diseases in hemato-oncological high-risk patients: a web-based non-interventional trial in four large university hospitals in Germany.

INTRODUCTION: Treatment indications of new antifungals in clinical practice often deviate from the strict criteria used in controlled clinical trials. Under routine clinical conditions, beneficial and adverse effects, not previously described in clinical trials may be observed. The aim of this study was to describe customary prescription and treatment strategies of micafungin (MCFG). METHODS: A registry was set up on www.ClinicalSurveys.net and physicians were invited to provide retrospective information on cases they had treated with MCFG. Documentation comprised demographic information, underlying disease, effectiveness, safety, and tolerability of MCFG. RESULTS: A total of 125 episodes of patients hospitalized between September 2009 and February 2012 were documented, of which 7 had to be excluded because of incomplete documentation. The most common risk factors of patients were hematological malignancy (n = 116, 98.3%) and antibiotic treatment >3 days (n = 115, 97.5%). MCFG was administered as prophylaxis in 106 (89.9%) patients. Median duration of MCFG application as prophylaxis was 21 days (range: 3-78); 53 of the patients (50%) received a dose of 50 mg, while the other 53 (50%) received 100 mg/day. For the different doses, prophylactic outcome was rated as success in 42 (79.2%) vs. 52 (98.1%; P = 0.004) patients. Fifty-five patients (51.9%) were treated with posaconazole before initiation of MCFG. Four patients (7.5%) developed a proven invasive fungal disease (IFD) while being treated with 50 mg MCFG, compared to no patient treated with 100 mg (P = 0.118). At the end of MCFG prophylaxis, 24 (22.6%) patients were switched to fluconazole and 64 (60.3%) patients to posaconazole. CONCLUSION: Our study shows clinical effectiveness of MCFG prophylaxis with low rates of breakthrough fungal infections. In most cases, MCFG was part of a multi-modal antifungal prophylactic strategy. Investigators reported fewer proven IFDs in patients receiving therapeutic doses of MCFG as prophylaxis.

Movement of the Rieske iron-sulfur protein in the p-side bulk aqueous phase: effect of lumenal viscosity on redox reactions of the cytochrome b6f complex.

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.

Low-grade metaplastic carcinoma of the thymus.

AIMS: Five cases of a characteristic low-grade thymic epithelial tumour are described that we suggest calling metaplastic carcinoma of the thymus. METHODS AND RESULTS: The patients' ages ranged from 44 to 71 (mean 56.2) years. Four of the patients were male. Three of five tumours showed invasion into mediastinal fat or pleura but, otherwise, all were well circumscribed. No metastases were present. Histologically, the tumours showed a biphasic pattern with solid carcinomatous areas merging gradually with a spindle cell component. Lymphocytes were rare. Cytological atypia and mitotic activity were variable in the solid areas, but slight or absent in the spindle cell component. On immunohistochemistry, the tumours showed expression of cytokeratin, vimentin and/or epithelial membrane antigen, both in the carcinomatous and spindle cell components. In two cases, actin expression was also present in both components. In one case, chromogranin, S100 protein, glial fibrillary acidic protein and neuron-specific enolase were expressed in at least some cells of both components. None of the patients had myasthenia gravis. All patients are alive without evidence of recurrence or metastasis. CONCLUSION: Metaplastic carcinoma of the thymus is a distinct clinicopathological entity that should be distinguished from the usually benign medullary thymomas and from the clinically aggressive carcinosarcomas and sarcomatoid carcinomas.

Two distinct states of the thylakoid bf complex.

Under normal physiological conditions the state of the cyt bf complex is characterized by rapid reoxidation kinetics of cyt b-563 following flash-illumination. It is known that these kinetics are dramatically slowed down under oxidizing conditions. Here we show that this slow-down of cyt b-563 oxidation is the consequence of a relatively slow (half-time of several minutes) transformation of the cyt bf complex into a distinctly different state (termed state-s). Reversal to the normal state requires strong reductive treatment or light-induced electron transport. The results are in line with a recent model of functional cyt bf dimers [Cramer et al., Annu. Rev. Plant Physiol. Plant Mol. Biol. 47 (1996), 477-5081, if it is assumed that state-s reflects the monomeric state of the bf complex.

Characterisation of a H2O 2-oxidisable cytochrome b-559 in intact chloroplasts with a new type of LED Array Spectrophotometer.

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.