Deleterious and Adaptive Mutations in Plant Germplasm Conserved Ex Situ.

Conserving more than 7 million plant germplasm accessions in 1,750 genebanks worldwide raises the hope of securing the food supply for humanity for future generations. However, there is a genetic cost for such long-term germplasm conservation, which has been largely unaccounted for before. We investigated the extent and variation of deleterious and adaptive mutations in 490 individual plants representing barley, wheat, oat, soybean, maize, rapa, and sunflower collections in a seed genebank using RNA-Seq technology. These collections were found to have a range of deleterious mutations detected from 125 (maize) to 83,695 (oat) with a mean of 13,537 and of the averaged sample-wise mutation burden per deleterious locus from 0.069 to 0.357 with a mean of 0.200. Soybean and sunflower collections showed that accessions acquired earlier had increased mutation burdens. The germplasm with more years of storage in several collections carried more deleterious and fewer adaptive mutations. The samples with more cycles of germplasm regeneration revealed fewer deleterious and more adaptive mutations. These findings are significant for understanding mutational dynamics and genetic cost in conserved germplasm and have implications for long-term germplasm management and conservation.

Highly Mesoporous Zr-Based MOF-Fabric Composites: A Benign Approach for Expeditious Degradation of Chemical Warfare Agents and Simulants.

Recent research has demonstrated the degradation of organophosphonates through hydrolysis using microporous UiO-66-NH2-fabric composites. Yet, challenges remain due to the limitations of organophosphonates accessing active sites in large, engineered granules. To address this, an innovative approach to integrate mesoporous UiO-66-NH2 onto various fabrics is provided, thereby overcoming previous mass transfer limitations. Mesoporosity in the UiO-66-NH2-fabric is attributed to the amphoteric cocamidopropylbetaine (CAPB) surfactant which templates the mesochannel construction. Unexpectedly, because the synthesis is aqueous, benign, low temperature (60°C), and avoids strong acids and toxic solvents, it is compatible with fragile supports such as untreated cotton. The UiO-66-NH2-fabric composite formed using treated polypropylene (PP) attains a BET specific surface area of 360 m2 g-1 comp. Remarkably, the mesoporous UiO-66-NH2-composites exhibit a pore volume as large as 0.2 cm3 g-1 comp, 33% in the mesoporous range, which is higher than other previous reports. Practically, the mesoporous UiO-66-NH2-treated PP composite enhances the rate of methyl paraoxon (DMNP) degradation, showing a t1/2 value that is 15 times faster than microporous UiO-66-NH2 composites measured under the same conditions. Similar trends are observed in the degradation of actual nerve agents. These composites hold significant potential across diverse applications, including filtration, protection, and catalysis.

Monodisperse Cyclic Polymer Mechanochemistry: Scission Kinetics and the Dynamic Memory Effect with Ultrasonication and Ball-Mill Grinding.

A series of monodisperse cyclic and linear poly(d,l-lactide)s (c-PLA and l-PLA, respectively) were prepared with various degrees of polymerization (DP) using an iterative convergent synthesis approach. The absence of a molecular weight distribution provided us a chance to study their mechanochemical reactivity without obstructions arising from the size distribution. Additionally, we prepared l- and c-PLAs with identical DPs, which enabled us to attribute differences in scission rates to the cyclic polymer architecture alone. The polymers were subjected to ultrasonication (US) and ball-mill grinding (BMG), and their degradation kinetics were explored. Up to 9.0 times larger scission rates were observed for l-PLA (compared to c-PLA) with US, but the difference was less than 1.9 times with BMG. Fragmentation requires two backbone scission events for c-PLA, and we were able to observe linear intermediates (formed after a single scission) for the first time. We also developed a new method of studying the dynamic memory effect in US by characterizing and comparing the daughter fragment molecular weight distributions of l- and c-PLAs. These results provide new insights into the influence of the cyclic polymer architecture on mechanochemical reactions as well as differences in reactivity observed with US and BMG.

BioADAPT-MRC: adversarial learning-based domain adaptation improves biomedical machine reading comprehension task.

MOTIVATION: Biomedical machine reading comprehension (biomedical-MRC) aims to comprehend complex biomedical narratives and assist healthcare professionals in retrieving information from them. The high performance of modern neural network-based MRC systems depends on high-quality, large-scale, human-annotated training datasets. In the biomedical domain, a crucial challenge in creating such datasets is the requirement for domain knowledge, inducing the scarcity of labeled data and the need for transfer learning from the labeled general-purpose (source) domain to the biomedical (target) domain. However, there is a discrepancy in marginal distributions between the general-purpose and biomedical domains due to the variances in topics. Therefore, direct-transferring of learned representations from a model trained on a general-purpose domain to the biomedical domain can hurt the model's performance. RESULTS: We present an adversarial learning-based domain adaptation framework for the biomedical machine reading comprehension task (BioADAPT-MRC), a neural network-based method to address the discrepancies in the marginal distributions between the general and biomedical domain datasets. BioADAPT-MRC relaxes the need for generating pseudo labels for training a well-performing biomedical-MRC model. We extensively evaluate the performance of BioADAPT-MRC by comparing it with the best existing methods on three widely used benchmark biomedical-MRC datasets-BioASQ-7b, BioASQ-8b and BioASQ-9b. Our results suggest that without using any synthetic or human-annotated data from the biomedical domain, BioADAPT-MRC can achieve state-of-the-art performance on these datasets. AVAILABILITY AND IMPLEMENTATION: BioADAPT-MRC is freely available as an open-source project at https://github.com/mmahbub/BioADAPT-MRC. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Potentially preventable hospitalisations in rural community-dwelling patients.

BACKGROUND: Potentially preventable hospitalisations (PPH) are a common occurrence. Knowing the factors associated with PPH may allow high-risk patients to be identified and healthcare resources to be better allocated, and these factors may differ between urban and rural locations. AIM: To determine factors associated with PPH in an Australian rural population. METHODS: A retrospective review of admitted patients' demographic and clinical data was used to describe and model the factors associated with PPH, using an age- and sex-matched control group of non-admitted patients. This study is based in a multi-site rural general practice, Tasmania. The study included patients aged ≥18 years residing in the Huon-Bruny Island region of Tasmania, who were active patients at a rural general practice and were admitted to a public hospital for a PPH between 1 July 2016 and 30 June 2019. Main outcome measure is overnight admission to hospital for a PPH. RESULTS: Predictors with a significant odds ratio (OR) in the final model were being single/unmarried (OR 2.43; 95% confidence interval (CI) 1.38-4.28), higher Charlson Comorbidity Index score (OR 1.40; 95% CI 1.13-1.74) and the number of general practice visits in the preceding 12 months (OR 1.09; 95% CI 1.05-1.14). CONCLUSIONS: This study found that being single and having a higher comorbidity burden were the strongest independent risk factors for PPH in a rural population. Demographic and socioeconomic factors appeared to be as, if not more, important than medical factors and warrant attention when considering the design of programmes to reduce PPH risk in rural communities.

Impact of pharmacist interventions provided in the emergency department on quality use of medicines: a systematic review and meta-analysis.

BACKGROUND: Pharmacists have an increasing role as part of the emergency department (ED) team. However, the impact of ED-based pharmacy interventions on the quality use of medicines has not been well characterised. OBJECTIVE: This systematic review aimed to synthesise evidence from studies examining the impact of interventions provided by pharmacists on the quality use of medicines in adults presenting to ED. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE and CINAHL. Two independent reviewers screened titles/abstracts and reviewed full texts. Studies that compared the impact of interventions provided by pharmacists with usual care in ED and reported medication-related primary outcomes were included. Cochrane Risk of Bias-2 and Newcastle-Ottawa tools were used to assess the risk of bias. Summary estimates were pooled using random-effects meta-analysis, along with sensitivity and sub-group analyses. RESULTS: Thirty-one studies involving 13 242 participants were included. Pharmacists were predominantly involved in comprehensive medication review, advanced pharmacotherapy assessment, staff and patient education, identification of medication discrepancies and drug-related problems, medication prescribing and co-prescribing, and medication preparation and administration. The activities reduced the number of medication errors by a mean of 0.33 per patient (95% CI -0.42 to -0.23, I2=51%) and the proportion of patients with at least one error by 73% (risk ratio (RR)=0.27, 95% CI 0.19 to 0.40, I2=85.3%). The interventions were also associated with more complete and accurate medication histories, increased appropriateness of prescribed medications by 58% (RR=1.58, 95% CI 1.21 to 2.06, I2=95%) and quicker initiation of time-critical medications. CONCLUSION: The evidence indicates improved quality use of medicines when pharmacists are included in ED care teams. PROSPERO REGISTRATION NUMBER: CRD42020165234.

Controlled Living Cascade Polymerization of Polycyclic Enyne Monomers: Leveraging Complete Degradability for a Stereochemical and Structural Investigation.

Cascade polymerizations recently gained significant attention due to their use of unique transformations, involving multiple bond making and/or breaking steps, when converting monomers to repeat units. However, designing complex cascade polymerizations which proceed in a controlled manner is very challenging. Various side reactions can hamper polymerization performance and the efficiency of the cascade. In this work, we explore a metathesis-based cascade polymerization of unique polycyclic enyne monomers, which contain a terminal alkyne and two cyclic alkenes. By modifying the monomer's stereochemistry, linkers, and ring types, we were able to modulate the polymerization performance and the extent to which a complete cascade reaction occurs. Upon subjecting the resulting polymers to mild acidic conditions and analyzing the degradation products, we were able to calculate the percentage of repeat units derived from a complete cascade reaction (termed the cascade efficiency). In addition to identifying how various structural parameters in the monomer influence the success of a cascade polymerization, we were able to achieve controlled living cascade polymerizations of multiple monomers with >99% cascade efficiency and produce various block copolymers.

Fabrication of Multifunctional Electronic Textiles Using Oxidative Restructuring of Copper into a Cu-Based Metal-Organic Framework.

This paper describes a novel synthetic approach for the conversion of zero-valent copper metal into a conductive two-dimensional layered metal-organic framework (MOF) based on 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) to form Cu3(HHTP)2. This process enables patterning of Cu3(HHTP)2 onto a variety of flexible and porous woven (cotton, silk, nylon, nylon/cotton blend, and polyester) and non-woven (weighing paper and filter paper) substrates with microscale spatial resolution. The method produces conductive textiles with sheet resistances of 0.1-10.1 MΩ/cm2, depending on the substrate, and uniform conformal coatings of MOFs on textile swatches with strong interfacial contact capable of withstanding chemical and physical stresses, such as detergent washes and abrasion. These conductive textiles enable simultaneous detection and detoxification of nitric oxide and hydrogen sulfide, achieving part per million limits of detection in dry and humid conditions. The Cu3(HHTP)2 MOF also demonstrated filtration capabilities of H2S, with uptake capacity up to 4.6 mol/kgMOF. X-ray photoelectron spectroscopy and diffuse reflectance infrared spectroscopy show that the detection of NO and H2S with Cu3(HHTP)2 is accompanied by the transformation of these species to less toxic forms, such as nitrite and/or nitrate and copper sulfide and Sx species, respectively. These results pave the way for using conductive MOFs to construct extremely robust electronic textiles with multifunctional performance characteristics.

Switching of oral anticoagulants in patients with nonvalvular atrial fibrillation: A narrative review.

Approval of direct-acting oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF) was an important milestone, providing a wider range of treatment options and creating the possibility for drug switching after initiation. In addition to improved utilisation of oral anticoagulants (OACs) for stroke prevention, reports of switching among OACs are growing in the literature; switching may influence clinical outcomes, healthcare costs and patient satisfaction. This review aimed to summarise the current literature on the pattern of OAC switching in patients with AF, including reasons for switching and clinical consequences following switching. A literature search was conducted in PubMed, Scopus and Embase on 27 June 2020. We included 39 articles published after 2013, following the introduction of apixaban. The review found that switching among OACs was common in clinical practice, significantly varying with the type of OAC. Studies reporting the reason for switching and clinical outcomes were comparatively limited. The decision to switch was often related to safety issues (usually bleeding), poor anticoagulation control and ease of use. Patient characteristics, clinical conditions and drug interactions were found to be associated with switching from OACs. Findings regarding bleeding outcomes following switching were inconsistent, possibly confounded by the rationale for switching and the switching protocol. Noting the limited number of studies included and their relatively short follow-up periods, switching did not have a significant impact on the risk of stroke and other thrombotic outcomes. Further prospective studies are needed to understand better potential rationales for switching and the clinical outcomes.

Efficacy and safety of remdesivir in hospitalised COVID-19 patients: a systematic review and meta-analysis.

PURPOSE: This review was aimed to synthesise the best available evidence on the effectiveness and safety of remdesivir in the treatment of moderate to severe COVID-19. METHOD: Randomised controlled trials (RCTs) and observational studies reporting the effectiveness and safety of remdesivir were searched via databases and other sources from December 2019 to December 2020. Two independent reviewers performed literature screening, data extraction and assessment of risk bias. Seven studies involving 3686 patients were included. RESULTS: Treatment with remdesivir was associated with an increase in clinical recovery rate by 21% (RR 1.21; 95% CI 1.08-1.35) on day 7 and 29% (RR 1.29; 95% CI 1.22-1.37) on day 14. The likelihoods of requiring high-flow supplemental oxygen and invasive mechanical ventilation in the remdesivir group were lower than in the placebo group by 27% (RR 0.73; 95% CI 0.54-0.99) and 47% (RR 0.53; 95% CI 0.39-0.72), respectively. Remdesivir-treated patients showed a 39% (RR 0.61; 95% CI 0.46-0.79) reduction in the risk of mortality on day 14 compared to the control group; however, there was no significant difference on day 28. Serious adverse effects (SAEs) were significantly less common in patients treated with remdesivir, with an absolute risk difference of 6% (RD -0.06; 95% CI -0.09 to -0.03). CONCLUSION: Despite conditional recommendation against its use, remdesivir could still be effective in early clinical improvement; reduction of early mortality and avoiding high-flow supplemental oxygen and invasive mechanical ventilation among hospitalised COVID-19 patients. Remdesivir was also well tolerated without significant SAEs compared to placebo, yet available evidence from clinical studies support the need to conduct close monitoring.

Effectiveness of Quality Incentive Payments in General Practice (EQuIP-GP) cluster randomized trial: impact on patient-reported experience.

BACKGROUND: Relational continuity, 'a therapeutic relationship between a patient and provider/s that spans health care events', has been associated with improved patient outcomes. OBJECTIVES: To evaluate whether an intervention incorporating patient enrolment and a funding model for higher-risk patients influenced patient-reported experience measures, particularly relational continuity. METHODS: Cluster-randomized controlled trial over 12 months (1 August 2018-31 July 2019). Participating patients within intervention practices were offered enrolment with a preferred general practitioner, a minimum of 3 longer appointments, and review within 7 days of hospital admission or emergency department attendance. Intervention practices received incentives for longer consultations (dependent on reducing unnecessary prescriptions and tests), early post-hospital follow-up, and hospitalization reductions. The primary outcome was patient-reported relational continuity, measured by the Primary Care Assessment Tool Short Form. RESULTS: A total of 774 patients, aged 18-65 years with a chronic illness or aged over 65 years, from 34 general practices in metropolitan, regional, and rural Australia across 3 states participated. Response rates for questionnaires were >90%. From a maximum of 4.0, mean baseline scores for relational continuity were 3.38 (SE 0.05) and 3.42 (SE 0.05) in control and intervention arms, respectively, with no significant between-group differences in changes pre-post trial. There were no significant changes in other patient-focussed measures. CONCLUSION: Patient-reported relational continuity was high at baseline and not influenced by the intervention, signalling the need for caution with policies incorporating patient enrolment and financial incentives. Further research is required targeting at-risk patient groups with low baseline engagement with primary care.

Relational continuity, 'a therapeutic relationship between a patient and provider/s that spans health care events', has been associated with improved patient outcomes. This study aimed to evaluate whether patient enrolment with a preferred general practitioner (GP) and a funding model for higher-risk patients influenced patient-reported experience measures, particularly relational continuity. The trial was randomized by practice and ran over 12 months (1 August 2018­31 July 2019). Participating patients within intervention practices were offered enrolment with a preferred GP, a minimum of 3 longer appointments, and review within 7 days of hospital discharge. Intervention practices received incentives for longer consultations (with quality improvements), early post-hospital follow-up, and hospitalization reductions. We measured patient experience using the Primary Care Assessment Tool­Short Form at baseline and completion. A total of 774 patients, aged 18­65 years with a chronic illness or aged over 65 years, from 34 general practices in metropolitan, regional, and rural Australia participated. Patient-reported relational continuity was high at baseline and not influenced by the intervention. There were no significant changes in other patient-focussed measures. We advise caution with policies incorporating patient enrolment and financial incentives. Further research is required targeting at-risk patient groups with low baseline engagement with primary care.

Self-reported medication adherence measurement tools: Some options to avoid a legal minefield.

WHAT IS KNOWN AND OBJECTIVE: Self-report questionnaires are used to measure medication adherence, often times both clinically and for research purposes. Despite the presence of several published tools, some may have prohibitive licensure and fee requirements, which researchers should be aware of prior to using them. This paper presents a summary of selected self-report measures, which have been developed and validated in various health conditions and can be used free of cost. COMMENT: Our review identified self-report tools that are valid to measure medication adherence in different chronic health conditions. Most of these tools measure both intentional and unintentional non-adherence and have shown good correlation with relevant clinical outcomes. WHAT IS NEW AND CONCLUSION: Given the potential copyright risks associated with using some of the self-report measures of adherence, an improved awareness and understanding of the available self-report questionnaires will better facilitate the decision by researchers to select appropriate tools relevant to their studies.

Elevated mutation and selection in wild emmer wheat in response to 28 years of global warming.

Global warming has been documented to threaten wild plants with strong selection pressures, but how plant populations respond genetically to the threats remains poorly understood. We characterized the genetic responses of 10 wild emmer wheat (Triticum dicoccoides Koern.; WEW) populations in Israel, sampling them in 1980 and again in 2008, through an exome capture analysis. It was found that these WEW populations were under elevated selection, displayed reduced diversity and temporal divergence, and carried increased mutational burdens forward. However, some populations still showed the ability to acquire beneficial alleles via selection or de novo mutation for future adaptation. Grouping populations with mean annual rainfall and temperature revealed significant differences in most of the 14 genetic estimates in either sampling year or over the 28 y. The patterns of genetic response to rainfall and temperature varied and were complex. In general, temperature groups displayed more temporal differences in genetic response than rainfall groups. The highest temperature group had more deleterious single nucleotide polymorphisms (dSNPs), higher nucleotide diversity, fewer selective sweeps, lower differentiation, and lower mutational burden. The least rainfall group had more dSNPs, higher nucleotide diversity, lower differentiation and higher mutational burden. These characterized genetic responses are significant, allowing not only for better understanding of evolutionary changes in the threatened populations, but also for realistic modeling of plant population adaptability and vulnerability to global warming.

Environmentally Benign Biosynthesis of Hierarchical MOF/Bacterial Cellulose Composite Sponge for Nerve Agent Protection.

The fabrication of MOF polymer composite materials enables the practical applications of MOF-based technology, in particular for protective suits and masks. However, traditional production methods typically require organic solvent for processing which leads to environmental pollution, low-loading efficiency, poor accessibility, and loss of functionality due to poor solvent resistance properties. For the first time, we have developed a microbial synthesis strategy to prepare a MOF/bacterial cellulose nanofiber composite sponge. The prepared sponge exhibited a hierarchically porous structure, high MOF loading (up to ≈90 %), good solvent resistance, and high catalytic activity for the liquid- and solid-state hydrolysis of nerve agent simulants. Moreover, the MOF/ bacterial cellulose composite sponge reported here showed a nearly 8-fold enhancement in the protection against an ultra-toxic nerve agent (GD) in permeability studies as compared to a commercialized adsorptive carbon cloth. The results shown here present an essential step toward the practical application of MOF-based protective gear against nerve agents.

Immobilized Regenerable Active Chlorine within a Zirconium-Based MOF Textile Composite to Eliminate Biological and Chemical Threats.

The most recent global health crisis caused by the SARS-CoV-2 outbreak and the alarming use of chemical warfare agents highlight the necessity to produce efficient protective clothing and masks against biohazard and chemical threats. However, the development of a multifunctional protective textile is still behind to supply adequate protection for the public. To tackle this challenge, we designed multifunctional and regenerable N-chlorine based biocidal and detoxifying textiles using a robust zirconium metal-organic framework (MOF), UiO-66-NH2, as a chlorine carrier which can be easily coated on textile fibers. A chlorine bleaching converted the amine groups located on the MOF linker to active N-chlorine structures. The fibrous composite exhibited rapid biocidal activity against both Gram-negative bacteria (E. coli) and Gram-positive bacteria (S. aureus) with up to a 7 log reduction within 5 min for each strain as well as a 5 log reduction of SARS-CoV-2 within 15 min. Moreover, the active chlorine loaded MOF/fiber composite selectively and rapidly degraded sulfur mustard and its chemical simulant 2-chloroethyl ethyl sulfide (CEES) with half-lives less than 3 minutes. The versatile MOF-based fibrous composite designed here has the potential to serve as protective cloth against both biological and chemical threats.

The global prevalence and trend of human intestinal carriage of ESBL-producing Escherichia coli in the community.

OBJECTIVES: Intestinal colonization by ESBL Escherichia coli and its association with community-acquired MDR infections is of great concern. This review determined the worldwide prevalence of human faecal ESBL E. coli carriage and its trend in the community over the past two decades. METHODS: A systematic literature search was conducted using PubMed, EMBASE and Google Scholar to retrieve articles published between 1 January 2000 and 13 February 2020 that contained data on the prevalence of faecal carriage of ESBL E. coli among healthy individuals. A cumulative (for the whole period) meta-analysis was used to estimate the global and regional pooled prevalence rates. Articles were grouped into study periods of 3 years, and subgroup meta-analyses were undertaken to examine the global pooled prevalence over time. RESULTS: Sixty-two articles covering 29 872 healthy persons were included in this meta-analysis. The cumulative (2003-18) global pooled prevalence of ESBL E. coli intestinal carriage in the community was 16.5% (95% CI 14.3%-18.7%; P  <  0.001). The pooled prevalence showed an upward trend, increasing from 2.6% (95% CI 1.6%-4.0%) in 2003-05 to 21.1% (95% CI 15.8%-27.0%) in 2015-18. Over the whole period, the highest carriage rate was observed in South-East Asia (27%; 95% CI 2.9%-51.3%), while the lowest occurred in Europe (6.0%; 95% CI 4.6%-7.5%). CONCLUSIONS: Globally, an 8-fold increase in the intestinal carriage rate of ESBL E. coli in the community has occurred over the past two decades. Prevention of its spread may require new therapeutic and public health strategies.

Variation in the pharmacokinetics of glucosamine in healthy individuals.

OBJECTIVES: Clinical trial data for the efficacy of glucosamine in OA are conflicting. Reportedly, Rotta-manufactured glucosamine products are more likely to be effective, and a possible explanation is greater bioavailability than other brands. Specifically, the aim was to compare the steady-state pharmacokinetics of Rotta- and non-Rotta-manufactured glucosamine products in healthy volunteers and examine the interindividual variability. METHODS: In a crossover design, healthy adult participants ingested 1500 mg/day of a Rotta (DONA powder sachets; imported by Mylan Health, Carole Park, QLD, Australia) and a non-Rotta (glucosamine sulphate 1500 mg one-a-day tablet; Blackmores, Warriewood, NSW, Australia) glucosamine product/brand individually for 6 days. Blood samples were collected immediately before and for 12 h after the ingestion of the last dose of each brand and analysed to determine plasma levels of glucosamine. The pharmacokinetic parameters at steady state [including the minimum (Css min) and maximum (Css max) plasma concentration of glucosamine, time to reach Css max post-dosing (Tss max) and area under the plasma concentration vs time curve (AUCss 0-12)] for each brand were calculated and statistically compared. RESULTS: Fourteen participants [mean age 35.5 years (s.d. 8.8)] were recruited (64.2% males). No significant differences were observed in the pharmacokinetic parameters between the two brands. However, for both brands, the coefficient of variation for Css min, Tss max and AUCss 0-12 exceeded 20%, indicating considerable differences in the parameters between participants. No significant association of the pharmacokinetic parameters was observed with various dosing- and participant-related variables. CONCLUSION: Substantial interindividual differences in the absorption and elimination of glucosamine could be a cause of variable clinical outcomes in OA. TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (http://www.ANZCTR.org.au/ACTRN12618000699268p.aspx), number ACTRN12618000699268p.

Factors influencing oral anticoagulant use in patients newly diagnosed with atrial fibrillation.

BACKGROUND: We investigated factors that influenced oral anticoagulant (OAC) initiation and choice in Australian general practice patients newly diagnosed with AF. METHODS: Using an Australian nationally representative general practice dataset, MedicineInsight, we identified patients newly diagnosed with AF between January 2009 and April 2019. Logistic regression analyses were used to examine factors associated with OAC initiation and choice. RESULTS: A total of 63 212 patients with AF (53.7% males, mean age 72.4 years) were identified. Nearly two-thirds of these patients (40 854 [64.6%]) were initiated on an OAC, at a median time of 6 days after the documented diagnosis date. The proportion of patients who were initiated an OAC increased from 44.8% in 2009 to 72.2% in 2019 (P < .001). High risk of stroke (CHA2 DS2 -VASc, adjusted odds ratio (AOR), 4.39 [95% CI, 3.99-4.83]), low risk of bleeding (ORBIT, AOR, 1.87 [95% CI, 1.72-2.03]), not having a recorded history of dementia (AOR, 1.81 [95% CI, 1.65-1.98]) and male sex (AOR, 1.29 [95% CI, 1.22-1.35]) were independently associated with OAC initiation. Direct-acting oral anticoagulant (DOAC) use increased from 11.9% in 2011 to 94.0% of all OAC initiations in April 2019 (P < .001). CONCLUSIONS: The proportion of newly diagnosed patients with AF initiated on OAC increased markedly following the introduction of the DOACs. Of those initiated, 9 in 10 were receiving a DOAC at the end of the study period. There is potential underuse in women and individuals with dementia.

Stroke risk reassessment and oral anticoagulant initiation in primary care patients with atrial fibrillation: A ten-year follow-up.

AIM: To examine the change in stroke risk over time and determine the proportion of patients with atrial fibrillation (AF) who were initiated on an oral anticoagulant (OAC) as their stroke risk increased from low/moderate to high, using the Australian general practice data set, MedicineInsight. METHODS: A total of 2296 patients diagnosed with AF between 1 January 2007 and 31 December 2008, aged 18 years or older and not initiated on an OAC before 2009, were included. We assessed the change in stroke risk and the proportion of patients who had a recorded prescription of an OAC, each year from 1 January 2009 to 31 December 2018. RESULTS: At baseline, 23.9%, 22.9% and 53.2% were categorised as being at low (score = 0), moderate (score = 1) and high stroke risk (score ≥ 2), respectively, using the sexless CHA2 DS2 -VASc (CHA2 DS2 -VA) score. Overall, the CHA2 DS2 -VA score increased by a mean of 1.34 (95% confidence interval, 1.29-1.39) points over the study period. Nearly two-thirds of patients (65%, 412/632) whose stroke risk changed from baseline low/moderate to high were subsequently prescribed an OAC. The median (interquartile range) lag time from becoming high stroke risk to having OAC initiation was 2 (5) years. CONCLUSIONS: Nearly one-third of patients reclassified as being at high risk of stroke during the study period were not prescribed OAC therapy. Furthermore, the delay in OAC initiation following classification as being at high risk was a median of 2 years, suggesting that more frequent stroke reassessment is needed.

Doubly Protective MOF-Photo-Fabrics: Facile Template-Free Synthesis of PCN-222-Textiles Enables Rapid Hydrolysis, Photo-Hydrolysis and Selective Oxidation of Multiple Chemical Warfare Agents and Simulants.

New materials and chemical knowledge for improved personal protection are among the most pressing needs in the international community. Reported attacks using chemical warfare agents (CWAs,) including organophosphate soman (GD) and thioether mustard gas (HD) are driving research in field-deployable catalytic composites for rapid toxin degradation. In this work, we report simple template-free low temperature synthesis that enables for the first time, a deployable-structured catalytic metal-organic framework/polymer textile composite "MOF-fabric" showing rapid hydrolysis and oxidation of multiple active chemical warfare agents, GD and HD, respectively, and their simulants. Our method yields new zirconium-porphyrin based nano-crystalline PCN-222 MOF-fabrics with adjustable MOF loading and robust mechanical adhesion on low-cost nonwoven polypropylene fibers. Importantly, we describe quantitative kinetic analysis confirming that our MOF-fabrics are as effective as or better than analogous MOF powders for agent degradation, especially for oxidation. Faster oxidation using the MOF-fabrics is ascribed to the composite geometry, where active MOF catalysts are uniformly displayed on the MOF-textile enabling better reactant transport and reactive oxidant generation. Furthermore, we note the discovery of visible photo-activation of GD hydrolysis by a MOF-fabric, which is ascribed to oxidation at the active metal node site, significantly increasing the rate over that observed without illumination. These results provide important new insights into the design of future materials and chemical systems to protect military, first-responders, and civilians upon exposure to complex chemical toxins.