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Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss Syndrome, is a multisystem antineutrophil cytoplasmic antibody (ANCA) positive vasculitis, characterized by the presence of chronic rhinosinusitis, asthma and prominent peripheral blood eosinophilia. Although the most commonly involved organ is the lung, followed by the skin, EGPA can affect any organ system. Herein, we present the complicated case of an 18-year-old male patient with severe life-threatening EGPA, with central nervous system, cardiac and gasterointestinal involvement, which was resistant to initial treatment with glucocorticoids and cyclophosphamide. The patient responded well, achieving complete remission after the addition of rituximab and mepolizumab to glucocorticoids and cyclophosphamide.

Background Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. Methods In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. Findings From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). Interpretation When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. Funding US National Institutes of Health.

Objectives Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections. Methods Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 105 CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes. Results The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04–2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03–2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95–2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09–3.25). Conclusions In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection.

Surgical site infection (SSI) rates in low- and middle-income countries (LMICs) range from 8 to 30% of procedures, making them the most common healthcare acquired infection (HAI) with substantial morbidity, mortality, and economic impacts. Presented here is an approach to surgical site infection prevention based on surveillance and focused on five key areas as identified by international experts. These five areas include: Collecting valid, high-quality data; Linking HAIs to economic incapacity, underscoring the need to prioritize infection prevention activities; Implementing SSI surveillance within infection prevention and control (IPC) programs to enact structural changes, develop procedural skills, and alter healthcare worker behaviors; Priotiziation of IPC training for healthcare workers in LMICs to conduct broad-based surveillance coupled with the development and implementation of locally applicable IPC programs; Developing a highly accurate and objective international system for defining SSIs that can be translated globally in a straightforward manner. Finally, we present a clear, unambiguous framework for successful SSI guideline implementation that supports the development of sustainable IPC programs in LMICs. This entails: i) identifying index operations for targeted surveillance; ii) identifying IPC “champions” and empowering healthcare workers; iii) using multimodal improvement measures; iv) positioning hand hygiene programs as the basis for IPC initiatives; and v), use of telecommunication devices for surveillance and healthcare outcome follow-ups. Additionally, special considerations for pediatric SSIs, antimicrobial resistance development, and antibiotic stewardship programs are addressed.

Objectives We assessed the proportion of primary health care (PHC) randomized controlled trial (RCT) protocols published in peer-reviewed journals that published results in subsequent papers in peer-reviewed journals; and whether this proportion changed over time. Study Design and Setting We searched (last update June 2019) for RCTs published in peer-reviewed journals reporting primary outcome results for 620 protocols that were published up to 2014 and were retrieved in PubMed. We recorded the absolute number and the proportion of protocols with published results per year; and estimated whether the proportion changed over time. Results Of the 620 published protocols, 525 (85%) disseminated their results through a published RCT by June 2019. The number of published protocols was increasing over time especially after 2001. However, the proportion of protocols per year with published results in subsequent papers was decreasing over time after 2002. Specifically, the proportion ranged from 86% to 96% for protocols published until 2010 while for those published from 2011 onward ranged from 76% to 86%. Mean time from protocol to results publication was 39 months (95% CI 37, 41). Conclusion Almost one-sixth of PHC trial protocols published in peer-reviewed journals did not publish their results in subsequent papers.

This paper presents a cost-based TSO-DSO coordination model to quantify the value of local flexibility services and analyze its impact on the transmission grid expansion and the system operation. Flexibility is provided to the DC power flow transmission grid model by microgrids within the integrated AC power flow distribution grid model. The model's objective is to minimize the overall cost of transmission investments and procured flexibility and is achieved using a bilevel optimization approach where the power exchanges on all connected grid interfaces are controlled. Case studies using a combined test system of the IEEE RTS-96 transmission network interfacing multiple 33-bus distribution grids were performed to validate the model and assess the values and impacts of local flexibility on the transmission system expansion. The results showed that the proposed model modified the investment plan and dispatch of flexibility resources reducing the investment and operation cost of the transmission system.

Summary Background Colistin–carbapenem combinations are synergistic in vitro against carbapenem-resistant Gram-negative bacteria. We aimed to test whether combination therapy improves clinical outcomes for adults with infections caused by carbapenem-resistant or carbapenemase-producing Gram-negative bacteria. Methods A randomised controlled superiority trial was done in six hospitals in Israel, Greece, and Italy. We included adults with bacteraemia, ventilator-associated pneumonia, hospital-acquired pneumonia, or urosepsis caused by carbapenem-non-susceptible Gram-negative bacteria. Patients were randomly assigned (1:1) centrally, by computer-generated permuted blocks stratified by centre, to intravenous colistin (9-million unit loading dose, followed by 4·5 million units twice per day) or colistin with meropenem (2-g prolonged infusion three times per day). The trial was open-label, with blinded outcome assessment. Treatment success was defined as survival, haemodynamic stability, improved or stable Sequential Organ Failure Assessment score, stable or improved ratio of partial pressure of arterial oxygen to fraction of expired oxygen for patients with pneumonia, and microbiological cure for patients with bacteraemia. The primary outcome was clinical failure, defined as not meeting all success criteria by intention-to-treat analysis, at 14 days after randomisation. This trial is registered at ClinicalTrials.gov, number NCT01732250, and is closed to accrual. Findings Between Oct 1, 2013, and Dec 31, 2016, we randomly assigned 406 patients to the two treatment groups. Most patients had pneumonia or bacteraemia (355/406, 87%), and most infections were caused by Acinetobacter baumannii (312/406, 77%). No significant difference between colistin monotherapy (156/198, 79%) and combination therapy (152/208, 73%) was observed for clinical failure at 14 days after randomisation (risk difference −5·7%, 95% CI −13·9 to 2·4; risk ratio [RR] 0·93, 95% CI 0·83–1·03). Results were similar among patients with A baumannii infections (RR 0·97, 95% CI 0·87–1·09). Combination therapy increased the incidence of diarrhoea (56 [27%] vs 32 [16%] patients) and decreased the incidence of mild renal failure (37 [30%] of 124 vs 25 [20%] of 125 patients at risk of or with kidney injury). Interpretation Combination therapy was not superior to monotherapy. The addition of meropenem to colistin did not improve clinical failure in severe A baumannii infections. The trial was unpowered to specifically address other bacteria. Funding EU AIDA grant Health-F3-2011-278348.

Online disinhibition is a common phenomenon with negative implications among adolescents, but its correlates have been scarcely investigated from an integrative perspective. This study aimed to examine the relationship of two socially maladaptive personal characteristics, namely psychopathic traits and social anxiety, with online disinhibition. Furthermore, the effect of empathy (affective and cognitive) was examined through moderation analysis. The investigation was based on a context-dependent theoretical framework, according to which, the structural characteristics of cyberspace increase or decrease the expression of certain personal tendencies, thus differentiating an individual's behavior. Overall, 1097 Greek Junior High School students from Northern Greece voluntarily completed an anonymous self-report questionnaire. After construct validity was tested, a two-step latent moderated structural equation modeling was conducted. Results showed that online disinhibition correlated negatively with all variables except affective empathy. Cognitive empathy moderated only the effect of impulsive-irresponsible traits and social anxiety on online disinhibition. Overall, findings show that students with maladaptive personality characteristics have high propensity for online disinhibition. These results can contribute significantly in understanding the phenomenon, as well as in the design of prevention programs aiming at developing the cognitive empathy of impulsive and socially anxious adolescents.

In vitro and clinical data were analysed to evaluate the susceptibility profile of itraconazole in light of the new cut-off points. The in vitro activity of itraconazole was compared with that of eight comparators against 119 Candida bloodstream isolates from 2015 to 2018. Minimum inhibitory concentrations (MICs) were measured by the colorimetric MICRONAUT-S assay. The content of wells without any color change was sub-cultured to measure killing efficacy. No major differences were found against Candida albicans. Itraconazole, posaconazole and amphotericin B were the most active agents against Candida parapsilosis. Of the 32 isolates of C. parapsilosis that were resistant to fluconazole, 96.9%, 78.1% and 93.8% were susceptible to itraconazole, voriconazole and posaconazole, respectively. The ratio of the minimum fungicidal concentration (MFC) to the MIC of itraconazole was lower than for the other azoles against C. parapsilosis and C. glabrata. Itraconazole achieved greater inhibition over-time of the growth of C. parapsilosis than fluconazole. Seventy-three critically ill patients who were unresponsive to antibiotics received intravenous empirical treatment with itraconazole (n = 28) or comparators (n = 45). Case-control matching was conducted for severity, comorbidities, risk factors for candidemia, administered antibiotics and days of antifungal treatment. Breakthrough candidemia was found in 3.6% of patients treated with itraconazole and in 32.1% of patients treated with comparators (P: 0.020); breakthrough candidemia by C. parapsilosis was found in 3.6% and 28.6% of patients, respectively. Results indicate that itraconazole retains a valuable susceptibility profile against Candida isolates, particularly C. parapsilosis. This superior profile may explain the clinical efficacy in the occurrence of breakthrough candidemia and warrants further clinical investigation.

Cyber-bullying (CB) is a prevailing phenomenon among University students, but scarcely investigated, thus leaving its correlates largely unexplored. Recently, integrated theoretical models were proposed for the explanation of the phenomenon, investigating complex interactions between personal and contextual factors. The present study was purported to investigate the association between several individual and contextual variables (attachment, Big Five personality traits, Internet use frequency, problematic Internet use, οnline disinhibition, loneliness, psychopathology) and CB/Cyber-victimization (CV) among 175 Greek University undergraduates, based on the General Aggression Model. Results showed that participants who used the Internet more frequently scored higher in CB. Significant positive correlations were observed between both CB and CV with Neuroticism, loneliness, anxiety, hostility, online disinhibition, and Problematic Internet Use, and positive with Agreeableness. Furthermore, CB was negatively correlated with Conscientiousness and CV negatively with depression. CB was predicted by low Agreeableness, frequent Internet use and higher levels of negative outcomes when using the Internet, while CV was predicted by low Agreeableness, high Extraversion, high loneliness and high compulsive Internet use. Overall, findings of this study indicate that CB and CV may involve students who make problematic Internet use, have specific personality traits and face various social difficulties and psychopathological symptoms.

In this work we synthesized triple cation (A = Cs, FA, MA), mixed halide (X = I, Br, Cl) APbX3 compounds to develop perovskite solar cells (PSCs) with improved thermal stability as well as high power conversion efficiency. The effects of the cation combination and the mixing of halides in mesostructured PSCs have been thoroughly investigated. The presence of cesium results in greater stability, less impurities and higher reproducibility. Power conversion efficiencies of ∼17% and ∼13.5% were recorded for PSCs with I-Br and I-Cl compounds, respectively. Despite their lower efficiency, the I-Cl containing PSCs exhibit greater stability in ambient conditions.

Aim: Our study aimed to assess the generation of neutralizing antibodies elicited 14 days post-injection of each dose of the BNT162b2 in 401 Greek healthcare workers, 59 of whom were previously-infected. Methods: The SARS-CoV-2 IgG II Quant assay on the Architect System was employed to monitor titers of neutralizing IgG against the receptor-binding domain of the S1 subunit of the spike protein in participant-derived serum samples. Results: After the first dose, titers were found to fluctuate with age, marking a significant decline in the 50-60 age group, while dropping even further in participants aged over 60. This difference was surmounted following the second dose, as the fold-changes recorded were significantly higher in the 50-60 age group, while escalating in subjects aged over 60. After the second dose, the respective fold-change reached significance only among the uninfected, while being marginal in the seropositive group. The immune response of previously-infected subjects to the first dose was more intense than the respective response of the uninfected to the second dose. Conclusion: Our findings suggest the importance of the timely administration of the second dose in the wide age range of 20-67 of our study cohort, questioning however its value among the seropositive.

Background The best available treatment against carbapenemase-producing Enterobacteriaceae (CPE) is unknown. The objective of this study was to investigate the effect of appropriate therapy and of appropriate combination therapy on mortality of patients with bloodstream infections (BSIs) due to CPE. Methods In this retrospective cohort study, we included patients with clinically significant monomicrobial BSIs due to CPE from the INCREMENT cohort, recruited from 26 tertiary hospitals in ten countries. Exclusion criteria were missing key data, death sooner than 24 h after the index date, therapy with an active antibiotic for at least 2 days when blood cultures were taken, and subsequent episodes in the same patient. We compared 30 day all-cause mortality between patients receiving appropriate (including an active drug against the blood isolate and started in the first 5 days after infection) or inappropriate therapy, and for patients receiving appropriate therapy, between those receiving active monotherapy (only one active drug) or combination therapy (more than one). We used a propensity score for receiving combination therapy and a validated mortality score (INCREMENT-CPE mortality score) to control for confounders in Cox regression analyses. We stratified analyses of combination therapy according to INCREMENT-CPE mortality score (0–7 [low mortality score] vs 8–15 [high mortality score]). INCREMENT is registered with ClinicalTrials.gov, number NCT01764490. Findings Between Jan 1, 2004, and Dec 31, 2013, 480 patients with BSIs due to CPE were enrolled in the INCREMENT cohort, of whom we included 437 (91%) in this study. 343 (78%) patients received appropriate therapy compared with 94 (22%) who received inappropriate therapy. The most frequent organism was Klebsiella pneumoniae (375 [86%] of 437; 291 [85%] of 343 patients receiving appropriate therapy vs 84 [89%] of 94 receiving inappropriate therapy) and the most frequent carbapenemase was K pneumoniae carbapenemase (329 [75%]; 253 [74%] vs 76 [81%]). Appropriate therapy was associated with lower mortality than was inappropriate therapy (132 [38·5%] of 343 patients died vs 57 [60·6%] of 94; absolute difference 22·1% [95% CI 11·0–33·3]; adjusted hazard ratio [HR] 0·45 [95% CI 0·33–0·62]; p

Wealth uncertainty may be resolved before consumption in which case consumption is optimal. But if uncertainty remains at the consumption level, after allocative decisions are made, ex post relative consumption is suboptimal. Therefore, ex ante the consumer has to balance attitudes to risk with underlying preferences. We study this problem in the context of expected utility with preferences over two goods, one of which is subject to additive ex post uncertainty. State preferences determine the utility gambles, and attitudes to risk evaluate these gambles, in order to choose an optimal consumption gamble. We study how risk aversion interacts with preferences to determine the direction and size of comparative statics effects using lattice programming, monotone comparative statics, methods. Comparative statics depend on the evaluation of comparative utility loss along the distribution of uncertainty and lattice theoretic properties allow us to determine how these relate to preferences and consumption. With the global regularity imposed by LSE (quasi-supermodularity) properties in direct value lattices we study the comparative statics of comparative risk aversion, income and underlying risk. We give conditions for a more risk averse consumer to choose a less or more risky consumption bundle and show that the direct LSE property determines comparative statics under first order stochastic dominant changes in ex ante uncertainty. Extensive examples demonstrate.

The role of probiotics in the prevention of ventilator-associated pneumonia (VAP) remains inconclusive. The aim of this study was to assess the efficacy of a probiotic regimen for VAP prophylaxis in mechanically ventilated multi-trauma patients, intubated immediately after the injurious insult. In a randomized, placebo-controlled study enrolling multi-trauma patients, patients expected to require mechanical ventilation for >10 days were assigned at random to receive prophylaxis with a probiotic formula (n=59) or placebo (n=53). The probiotic formula was a preparation of Lactobacillus acidophilus LA-5 [1.75 × 109 colony-forming units (cfu)], Lactobacillus plantarum (0.5 × 109 cfu), Bifidobacterium lactis BB-12 (1.75 × 109 cfu) and Saccharomyces boulardii (1.5 × 109 cfu) in sachets. Each patient received two sachets twice daily for 15 days: one through the nasogastric tube and one spread on the oropharynx. The incidence of VAP was the primary endpoint. The incidence of other infections and sepsis, and the duration of hospital stay were the secondary endpoints. Administration of probiotics reduced the incidence of VAP [11.9% vs 28.3%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.13–0.92; P=0.034] and sepsis [6.8% vs 24.5%, odds ratio 0.22, 95% CI 0.07–0.74: P=0.016]. Furthermore, probiotic prophylaxis reduced the time of stay in the intensive care unit (ICU) and the length of hospital stay. The prophylactic use of probiotics with a combination of enteral and topical application to the oropharynx had a positive effect on the incidence of VAP and sepsis, as well as on ICU and total hospital stay in patients receiving protracted mechanical ventilation.

We report here on the crystal structure and physical properties of ((CH3)3S)2SnX6 (X = Cl, Br, I) compounds as well as the application of ((CH3)3S)2SnI6 in dye-sensitized solar cells. Powder X-ray diffraction and Rietveld analysis show that the materials form a cubic structure with a 0D network of [SnX6] octahedra, which can be considered as a defect variant (AB0.5X3) of the perovskite archetype (ABX3). The electronic band gaps of ((CH3)3S)2SnX6 were determined by UV–Vis reflectance spectroscopy at 4.1, 2.9 and 1.4 eV for X = Cl, Br, and I, respectively. The direct bandgap and its relative decrease in the order of light to heavy halide was independently verified by density-of-states calculations. According to Raman spectroscopy, the lattice vibrations also depend largely on the halogen atom. The air-stable and non-toxic ((CH3)3S)2SnI6 compound was incorporated in electrolyte-free, dye-sensitized solar cells based on the Z907 chromophore chemisorbed onto mesoporous titania electrodes. A power conversion efficiency of 5% is achieved for these photovoltaic devices, confirming efficient charge transport in the bulk ((CH3)3S)2SnI6 and hole extraction at the perovskite-Pt interface.

The spatial dynamics of the molluscan fauna associated with Cystoseira spp. assemblages of the upper sublittoral were analyzed, in a semi-enclosed gulf in the Aegean Sea, in April 2009. The faunal samples were collected by SCUBA diving from 4 locations along the coastline, 2 on each opposing side of the Pagasitikos gulf. A total of 1363 individuals belonging to 41 species were identified, with the gastropods being the dominant group. The most abundant and frequent species were Bittium reticulatum, Bittium latreillii and Alvania aspera. All feeding guilds were represented, with the most dominant being micrograzers followed by filter feeders. Molluscan community structure displayed significant spatial variation in terms of diversity and abundance. The hydrodynamic regime of the area seems to be a decisive factor that affects both the algal biomass and the molluscan abundance and distribution.