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Introduction: We aimed to investigate the risk factors for secondary lower respiratory tract fungal infection during acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methodology: A total of 466 AECOPD patients diagnosed from March 2019 to November 2020 were divided into infection (n = 48) and noninfection (n = 418) groups. The risk factors for lower respiratory tract fungal infection were screened by logistic regression analysis, and a nomogram prediction model was established. The discriminability was validated by area under the receiver operating characteristic curve (AUC) and C-index, calibration was validated by GiViTI calibration belt and Hosmer-Lemeshow test, and clinical validity was assessed by decision curve analysis (DCA) curve. Results: Thirty fungi strains were detected, including 18 strains of Candida albicans. Pulmonary heart disease, hypoalbuminemia, use of antibiotics within 3 months before admission, use time of antibiotics ≥ 14 d, invasive operation, blood glucose ≥ 11.10 mmol/L at admission, and procalcitonin (PCT) ≥ 0.5 ng/mL when diagnosed as fungal infection independent risk factors (p < 0.05). AUC was 0.891, indicating high discriminability of the model. The threshold probability in the DCA curve was set to 31.3%, suggesting that the model had clinical validity. Conclusions: We identified the independent risk factors for lower respiratory tract fungal infection in AECOPD patients. The established model has high discriminability and calibration. Immediate intervention is beneficial when the predicted risk exceeds 31.3%. [ABSTRACT FROM AUTHOR]

Whether real-world complex networks are scale free or not has long been controversial. Recently, in Broido and Clauset [A. D. Broido, A. Clauset, Nat. Commun. 10, 1017 (2019)], it was claimed that the degree distributions of real-world networks are rarely power law under statistical tests. Here, we attempt to address this issue by defining a fundamental property possessed by each link, the degree-degree distance, the distribution of which also shows signs of being power law by our empirical study. Surprisingly, although full-range statistical tests show that degree distributions are not often power law in real-world networks, we find that in more than half of the cases the degree- degree distance distributions can still be described by power laws. To explain these findings, we introduce a bidirectional preferential selection model where the link configuration is a randomly weighted, two-way selection process. The model does not always produce solid power-law distributions but predicts that the degree-degree distance distribution exhibits stronger power-law behavior than the degree distribution of a finitesize network, especially when the network is dense. We test the strength of our model and its predictive power by examining how real-world networks evolve into an overly dense stage and how the corresponding distributions change. We propose that being scale free is a property of a complex network that should be determined by its underlying mechanism (e.g., preferential attachment) rather than by apparent distribution statistics of finite size. We thus conclude that the degree-degree distance distribution better represents the scale-free property of a complex network. [ABSTRACT FROM AUTHOR]

Establishing long-distance quantum entanglement, i.e., entanglement transmission, in quantum networks (QN) is a key and timely challenge for developing efficient quantum communication. Traditional comprehension based on classical percolation assumes a necessary condition for successful entanglement transmission between any two infinitely distant nodes: they must be connected by at least a path of perfectly entangled states (singlets). Here, we relax this condition by explicitly showing that one can focus not on optimally converting singlets but on establishing concurrence--a key measure of bipartite entanglement. We thereby introduce a new statistical theory, concurrence percolation theory (ConPT), remotely analogous to classical percolation but fundamentally different, built by generalizing bond percolation in terms of "sponge-crossing" paths instead of clusters. Inspired by resistance network analysis, we determine the path connectivity by series and parallel rules and approximate higher-order rules via star-mesh transforms. Interestingly, we find that the entanglement transmission threshold predicted by ConPT is lower than the known classical-percolation-based results and is readily achievable on any series-parallel networks such as the Bethe lattice. ConPT promotes our understanding of how well quantum communication can be further systematically improved versus classical statistical predictions under the limitation of QN locality--a "quantum advantage" that is more general and efficient than expected. ConPT also shows a percolationlike universal critical behavior derived by finite-size analysis on the Bethe lattice and regular two-dimensional lattices, offering new perspectives for a theory of criticality in entanglement statistics. [ABSTRACT FROM AUTHOR]

In this work, a new D–A copolymer based on m-alkoxyphenyl substituted benzodithiophene (BDT-m-OP) as donor unit and benzo[1,2-c:4,5-c′]dithiophene-4,8-dione (BDD) as acceptor unit was designed and synthesized, in which selenophene unit as π-conjugated spacer was incorporated into the polymer backbone to broaden the absorption spectrum, enhance the charge transport properties, and even improve the photovoltaic properties. Compared with PBPD-Th with thiophene as π-conjugated spacer, PBPD-Se exhibits an evidently extended absorption spectrum and an enhanced hole mobility with a slightly raised HOMO energy level. The PBPD-Se:PC71BM-based PSCs exhibits a significantly improved PCE of 9.8% with an enhanced Jsc of 14.9 mA cm–2 and a slightly lower Voc of 0.90 V in comparison with a PCE of 8.4% with a Voc of 0.95 V and a Jsc of 12.4 mA cm–2 for PBPD-Th:PC71BM-based devices. These results indicate that the rational selection of π-conjugated spacer in the D–A copolymer backbone is very essential to achieve high efficiency PSCs. [ABSTRACT FROM AUTHOR]

Rivastigmine is approved in the USA for the treatment of mild to moderate Alzheimer's disease and Parkinson's disease dementia (PDD). Executive function (EF) deficits are a core symptom of PDD. The current objective was to investigate the effects of rivastigmine capsules versus placebo on EF in PDD, focusing on secondary outcome measures from a large, international, randomized, double-blind, placebo-controlled, 24-week trial (EXPRESS, CENA713B2311). Secondary outcomes included Delis-Kaplan Executive Function System (D-KEFS) measures of EF. Data from three D-KEFS subtests (Card Sorting, Letter Fluency, Color-Word Interference), plus the Symbol Digit Modalities Test were analyzed in the observed case (OC) population. Changes from baseline in the rivastigmine versus placebo groups were evaluated using the van Elteren test blocking for country. Of 541 patients in the EXPRESS study, 402, 71, 97, and 65 patients provided data for Letter Fluency, Card Sorting and Color-Word Interference subtests, and the Symbol Digit Modalities Test, respectively. On Letter Fluency, rivastigmine was associated with improvements in correct responses, set loss errors, and responses made (all P < 0.05), but not repetition errors. Higher Card Sorting recognition description score ( P= 0.03), and more correct substitutions on the Symbol Digit Modalities Test ( P= 0.02) were also recorded. Rivastigmine was associated with significant improvements over placebo on EF tests evaluating flexibility of thinking, problem solving and planning in patients with PDD. These findings support the hypothesis that rivastigmine may affect frontal subcortical circuits, which potentially contributes to observed clinical improvement associated with EF. [ABSTRACT FROM AUTHOR]

Aims: To investigate the effects of rivastigmine capsule 3–12 mg/day over 24 weeks on activities of daily living (ADLs) in patients with dementia associated with Parkinson’s disease (PDD). Methods: Post hocanalysis of a prospective, multicenter, randomized, double-blind, placebo-controlled trial in patients with PDD (≥50 years) randomized to rivastigmine 3–12 mg/day (capsules bid) or placebo over 24 weeks. This analysis was carried out with three subscales derived from a factor analysis of the 23 items in the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL) scale. These subscales were basic ADLs (10 items), high-level function ADLs (eight items) and autonomy ADLs (five items). Results: 541 patients were randomized (362 to rivastigmine, 179 to placebo) and 410 (75.8%) completed the study. Rivastigmine was associated with significantly better outcomes in basic ADLs (–0.5 ± 6.19 vs. –1.7 ± 5.46; p = 0.025; effect size 22.1%) and high-level function ADLs (0.1 ± 4.95 vs. –1.0 ± 4.49; p = 0.017; effect size 22.9%) compared with placebo, at week 24. Conclusion: In patients with PDD, treatment with rivastigmine may show beneficial effects on overall ADLs, as well as modest, statistically significant improvements in basic ADLs and high-level function ADLs. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

AbstractObjective:To investigate the tolerability and efficacy of the rivastigmine transdermal patch in patients with mild-to-moderate Alzheimers disease receiving concomitant memantine.Research design and methods:Post hoc analysis of a 25-week, randomized, prospective, open-label, parallel-group study. Patients receiving donepezil were switched to rivastigmine patches (4.6mg/24h) immediately or following a 7-day withdrawal for 4 weeks (core phase), before titrating up to 9.5mg/24h for a further 20-week extension phase. Prior memantine therapy was continued throughout. Clinical trial registration:clinicaltrials.gov. NCT00428389.Main outcome measures:Tolerability (adverse events [AEs], serious AEs [SAEs] and discontinuations) and efficacy (cognition, global functioning and activities of daily living [ADLs]) were assessed for the rivastigmine transdermal patch, with or without concomitant memantine.Results:Overall, 135 and 126 patients received rivastigmine with and without memantine, respectively. Of these, 122 (90.4) and 118 (93.7) patients with and without memantine, respectively, completed the core phase; 120 and 114 patients, respectively, entered the extension phase, and 90 (75.0) and 86 (75.4) completed the study. The incidences of AEs (73.3 vs. 67.5) and SAEs (10.4 vs. 7.1) were both slightly larger in patients receiving concomitant memantine, but the differences were not statistically significant (95 CIs: −5.2, 16.9 and −3.6, 10.1 for AEs and SEAs, respectively). The incidence of gastrointestinal AEs was low in both groups. Discontinuation due to AEs was higher in patients who received memantine (17.0 vs. 11.9). Changes in cognitive and global function were similar between groups. ADL scores worsened in both groups; significantly more in those treated with memantine.Conclusion:Use of the rivastigmine transdermal patch in patients on established memantine appears to be well-tolerated, with only modest, non-significant increases in AEs compared with monotherapy, and did not seem to affect cognition or global functioning adversely. [ABSTRACT FROM AUTHOR]

Background and Objectives: Transdermal patches provide non-invasive, continuous drug delivery, and offer significant potential advantages over oral treatments. With all transdermal treatments a proportion of patients will experience some form of skin reaction. The rivastigmine patch has been approved for the treatment of mild-to-moderate Alzheimer's disease (AD) since July 2007 in the US. The aim of the component of the trial reported here was to evaluate the skin tolerability of the rivastigmine transdermal patch in patients with mild-to-moderate AD. Methods: The pivotal IDEAL trial was a 24-week, randomized, double-blind, placebo-controlled, multicentre trial of the efficacy and tolerability of the rivastigmine transdermal patch in 1195 patients with mild-to-moderate AD. This was followed by a 28-week open-label extension. Although not prospectively defined as a secondary assessment, during both phases of the study the condition of the patients' skin at the application site was evaluated. These data are reviewed in this article. Results: During the 24-week, double-blind phase of the study, 89.6% of patients in the target 9.5 mg/24 h patch treatment group had recorded 'no, slight or mild' signs or symptoms for their most severe application-site reaction. Erythema and pruritus were the most commonly reported reactions. No patient in any patch treatment group experienced a skin reaction that was reported as a serious adverse event. In the 9.5mg/24 h treatment group, 2.4% of patients discontinued treatment due to an application-site reaction. During the 28-week open-label extension, the skin tolerability profile was similar to that seen in the double-blind phase. Overall, 3.7% of patients discontinued treatment due to application-site skin reactions. There was no indication that the severity of the skin reactions increased over time. Conclusion: Overall, the data support a favourable skin tolerability profile for the rivastigmine transdermal patch, and provide reassurance that the benefits of rivastigmine patch therapy for patients with AD are not confounded by significant skin irritation problems. Nevertheless, care should be taken to follow manufacturer's advice about patch application, such as daily rotation of the application site, to minimize the risk of skin reactions. [ABSTRACT FROM AUTHOR]

Introduction: Demographic and disease characteristics may impact response to psoriasis therapies. The objective of this study is to explore the safety and efficacy profile of secukinumab in North American (NA) versus non-NA patients with moderate to severe psoriasis. Methods: Data were pooled from four phase 3 studies of secukinumab. Secukinumab (300 and 150 mg) was administered at baseline, weeks 1, 2, and 3, then every 4 weeks from week 4 to 48. Results: Peak efficacy was observed at week 16 in NA and non-NA patients with secukinumab 300mg and secukinumab 150 mg, and disease clearance was maintained to week 52. At week 52 with secukinumab 300 mg, Psoriasis Area and Severity Index (PASI) 90/100 response was achieved by 62.9%/37.9% of NA patients, respectively, and 70.2%/42.0% of non-NA patients, respectively. At week 52 with secukinumab 150mg, PASI 90/100 response was achieved by 30.9%/17.5% of NA patients, respectively, and 53.9%/26.9% of non-NA patients, respectively. Response to secukinumab was rapid, and 50% reduction in mean PASI was achieved in both groups after 2.9 weeks with secukinumab 300mg and 3.7 weeks with secukinumab 150mg. Conclusion: Despite differences in baseline characteristics, the efficacy and safety of secukinumab were similar among NA and non-NA patients. [ABSTRACT FROM AUTHOR]

Two kinds of conjugated C3-symmetric perylene dyes, namely, triperylene hexaimides (TPH) and selenium-annulated triperylene hexaimides (TPH-Se), are efficiently synthesized. Both TPH and TPH-Se have broad and strong absorption in the region 300-600 nm together with suitable LUMO levels of about -3.8 eV. Single-crystal X-ray diffraction studies show that TPH displays an extremely twisted three-bladed propeller configuration and a unique 3D network assembly in which three PBI subunits in one TPH molecule have strong π-π intermolecular interactions with PBI subunits in neighboring molecules. The integration of selenophene to TPH endows TPH-Se with a more distorted propeller configuration and a more compact 3D network assembly due to the Se⋯O interactions. A single-crystal transistor confirms that both TPH and TPH-Se possess good electron-transport ability. TPH and TPH-Se acceptor-based solar cells show high power conversion efficiency of 8.28% and 9.28%, respectively, which mainly results from the combined properties of broad and strong absorption ability, appropriate LUMO level, desirable aggregation, high electron mobility, and good film morphology with the polymer donor. [ABSTRACT FROM AUTHOR]

Introduction The Severe Impairment Battery (SIB) is validated for assessing cognition in patients with severe dementia. The current analysis aimed to further investigate the cognitive efficacy of rivastigmine capsules, as assessed by SIB factor scores, in patients with moderately severe-to-severe Alzheimer's disease (AD). Methods This was a retrospective analysis of a 26-week, multicenter, randomized, double-blind, placebo-controlled study of oral rivastigmine conducted in Spain. Previously reported outcome measures included the full SIB. Current analyses examined calculated scores and effect sizes for the change from baseline at Week 26 on: newly defined SIB subscales (derived by a factor analysis of the 40 SIB items, using the PROC FACTOR function [SAS]); previously defined memory, language and praxis subscales (derived by previous factor analysis of the nine SIB domains); and the individual SIB items. Treatment differences were assessed. Results SIB data were provided by 104 rivastigmine-treated patients and 106 patients receiving placebo (Intent-To-Treat Last Observation Carried Forward population). Significantly less decline was observed on the previously defined memory and language subscales, and the newly defined working memory/memory subscale in rivastigmine-treated patients (all P < 0.05 versus placebo). Calculation of effect sizes demonstrated numerically greater efficacy of rivastigmine versus placebo on each of the subscales, and a broad range of SIB items; greatest effect sizes were observed on SIB items assessing the current month (effect size = 0.30) and digit span series (effect size = 0.33). Conclusions These data suggest the observed efficacy of rivastigmine in moderately severe-to-severe AD is likely a cumulative effect across a range of tasks. Rivastigmine demonstrates broad cognitive efficacy in this patient population. [ABSTRACT FROM AUTHOR]

AbstractBackground:Two sizes of rivastigmine patch (5 cm2and 10 cm2) are currently approved in the US and Europe, while a 20 cm2 rivastigmine patch has also been tested. A 15 cm2 rivastigmine patch may provide an optimal balance between efficacy and safety. Earlier studies have demonstrated the efficacy of rivastigmine in severe Alzheimer''s disease (AD), and supported the use of a higher dose patch in AD.Objective:The ACTION (ACTivities of daily living and cognitION) trial (Study CENA713DUS44) is designed to evaluate the efficacy and safety of low-dose versus high-dose rivastigmine transdermal patch in patients with severe AD.Methods:ACTION is a prospective, randomized, parallel-group, double-blind, multicenter study of patients (aged 50 years) with severe AD and a Mini-Mental State Examination score of 3–12. Novartis began recruitment in July 2009 and is conducting the trial in the United States. Patients are randomized to receive either a 5 cm2 (4.5 mg/24 h) or a 15 cm2 rivastigmine patch (13.3 mg/24 h) for 24 weeks. Patients receiving the 15 cm2 patch will be up-titrated over 8 weeks, via 5 and 10 cm2 patches. The primary efficacy outcomes include activities of daily living (ADLs), assessed with the Alzheimer''s Disease Cooperative Study – Activities of Daily Living – Severe Impairment Version (ADCS-ADL-SIV), and cognition, assessed with the Severe Impairment Battery (SIB). Secondary outcomes include behavior (Neuropsychiatric Inventory), global functioning (Alzheimer''s Disease Cooperative Study – Clinical Global Impression of Change), response rates, and safety.Conclusions:The ACTION trial examines the efficacy and tolerability of a 15 cm2 rivastigmine patch over a 24-week period in patients with severe AD. This is a novel trial in the development of rivastigmine, as it uses a design that does not include a placebo arm, is recruiting patients with severe AD, and includes an ADL measure as a co-primary efficacy variable.Clinical registration number:CENA713D US44. [ABSTRACT FROM AUTHOR]

Background: The Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) scale is widely used in Alzheimer trials. It assesses cognition, activities of daily living (ADLs), behavior and global functioning. To advance the understanding of relationships between the ADCS-CGIC and scores from other commonly used tools, this analysis investigated the ability of each domain to measure change. This was a hypothesis-forming study, designed to provide a basis for possible future research. Methods: This retrospective analysis used data from a 24-week, randomized, placebo-controlled trial [study ENA713D2320 (IDEAL)] that evaluated rivastigmine patches and capsules in AD patients. Results: At week 24, significant treatment effects versus placebo were seen on the ADCS-CGIC cognitive domain with rivastigmine 17.4 mg/24 h patch (p < 0.01), 9.5 mg/24 h patch (p = 0.02) and capsules (p < 0.01); similarly on the ADCS-CGIC ADL domain. The cognition portion of the CGIC correlated with the Alzheimer’s Disease Assessment Scale cognitive subscale and the ADL section with the ADCS-ADL trial measures. Variance ascribable to these tools was small, indicating that CGIC detects changes not measured by the domain-specific tools. Conclusions: The results of this post hoc analysis suggest that the ADCS-CGIC accurately reflects changes in cognitive and functional domains measured by other tools; it captures changes not assessed by domain-specific instruments. Cognitive alterations show greatest correlation with total CGIC. These results may assist in analyzing and interpreting CGIC results in other trials. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]