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OBJECTIVE: The authors compared the effect of 2 insertion methods, namely the conventional laryngeal mask airway (LMA) insertion and the index finger-assisted LMA insertion, on the incidence of complications associated with LMA Protector insertion. METHODS: The authors enrolled 300 patients, who underwent painless bronchoscopy. The patients ranged in age between 18 and 75 and were classified as American Society of Anesthesiologists grade I to III. They were randomly divided into 2 groups: a control group of 150 patients and an assisted group comprising 150 patients. LMA was inserted using the conventional and index finger-assisted insertion methods in both groups, respectively. The primary outcome was postoperative complications, such as oral mucosal injury and pharyngeal pain. Secondary outcomes included the success rate of first-time insertion, the incidence rate of inverse folding of LMA tips, oropharyngeal leak pressure (OLP), and other postoperative complications. RESULTS: Compared with the conventional LMA insertion method, index finger-assisted LMA insertion can significantly reduce the incidence rate of oral mucosal injury and pharyngeal pain, with fewer insertion failures. There was a statistically significant difference between the 2 groups in the visual field grading before adjustment for LMA alignment (P<0.0001). The conventional insertion method increased the likelihood of inverse folding of LMA tips. When the conventional insertion method was utilized, there was a significant difference in airway pressure and tidal volume before and after alignment under a fiberoptic bronchoscope (P<0.0001), but no significant difference in visual field grading and respiratory mechanics-related indicators. CONCLUSIONS: Index finger-assisted insertion can significantly reduce the incidence rate of LMA Protector-related complications and inverse folding of LMA tips.
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BACKGROUND: Critically ill patients with sepsis are predisposed to physiological changes that can reduce the probability of achieving target antibiotic exposures. Precision dosing software programs may be used to improve probability of obtaining these target exposures. OBJECTIVE: To quantify the accuracy of a precision dosing software program for predicting antibiotic concentrations as well as to assess the impact of using software predictions on actual dosing adjustments. PATIENTS AND METHODS: The software program ID-ODS was used to predict concentrations for piperacillin, meropenem and vancomycin using patient covariate data with and without the use of therapeutic drug monitoring (TDM) data. The impact of these predictions on actual dosage adjustments was determined by using software predicted concentrations versus measured concentrations. RESULTS: Software predictions for piperacillin and meropenem exhibited large bias that improved with the addition of TDM data (bias improved from -28.8 to -2.0 mg/L for piperacillin and -3.0 to -0.1 mg/L for meropenem). Dosing changes using predicted concentrations of piperacillin and meropenem with TDM data versus measured concentrations were matched on 89.2% (107/120) and 71% (9/69) occasions, respectively. Although vancomycin predictions demonstrated good accuracy with and without TDM, these findings were limited by our small sample size. CONCLUSION: These data demonstrate that precision dosing software programs may have scope to reasonably predict antibiotic concentrations in critically ill patients with sepsis. The addition of TDM data improves the predictive performance of the software for all three antibiotics and the ability to anticipate the correct dose change required.
Subject(s)
Anti-Bacterial Agents , Sepsis , Humans , Anti-Bacterial Agents/therapeutic use , Meropenem/therapeutic use , Vancomycin/therapeutic use , Critical Illness/therapy , Piperacillin/therapeutic use , Software , Sepsis/drug therapy , Drug MonitoringABSTRACT
The simple one-step reaction of [60]fullerene with α-monosubstituted acetaldehydes and primary amines in the presence of Mn(OAc)3·2H2O under air conditions afforded a series of novel N-substituted fulleropyrrolines with trisubstituted CîC bonds in moderate to good yields. The addition of Mn(OAc)3·2H2O played a crucial role in the successful synthesis of N-aryl fulleropyrrolines with trisubstituted CîC bonds, which would be extremely difficult to prepare by known methods as a result of the decreased nucleophilicity of arylamines due to the p-π conjugation effect. Intriguingly, arylamines displayed abnormally higher reactivity as compared with non-arylamines in the current reaction system by the observation of obviously decreased equivalent of Mn(OAc)3·2H2O, higher product yields, and lower reaction temperature probably due to the radical reaction mechanism initiated by Mn(OAc)3·2H2O. On the basis of experimental observations, a plausible formation pathway for N-substituted fulleropyrrolines with trisubstituted CîC bonds was proposed to elucidate the above-mentioned reaction process.
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A new coumestan named bavacoumestan D (1), together with five known compounds (2-6), was isolated from EtOAc-soluble extract of seeds of Psoralea corylifolia. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All compounds were evaluated for in vitro inhibitory activity against DGAT1, DGAT2 and α-glucosidase. Among them, compounds 1-2, 5-6 showed potential inhibitory activity on DGAT1 with IC50 values ranging from 52.3 ± 1.3 to 81.0 ± 1.0 µM. Compounds 1-3, 6 displayed the significant inhibitory activity on α-glucosidase with IC50 values ranging from 31.2 to 89.1 µM.[Formula: see text].
Subject(s)
Psoralea , Coumarins , Molecular Structure , SeedsABSTRACT
PURPOSE OF REVIEW: Malignant pleural mesothelioma (MPM) is a universally fatal illness with a rising incidence, particularly in developing countries. The diagnosis can be challenging and require repeated investigations with implications for the patient and healthcare system. RECENT FINDINGS: Distinguishing between benign/reactive and malignant mesothelial proliferations can be challenging. Cytological diagnosis of MPM from pleural fluid is as reliable as histological analysis of tissue biopsies in epithelioid MPM - an approach endorsed by the International Academy of Cytology. Identification of BRCA1-associated protein 1 (BAP1) and cyclin-dependent kinase inhibitor 2A (CDKN2A) gene mutations in MPM have led to the development of new ancillary tests that can streamline the diagnostic pathway. The prognostic values of these molecules are being investigated. Clinicians should be aware of the recently described BAP1 tumor predisposition syndrome and offer genetic investigations in potential patients. Routine use of prophylactic radiotherapy in MPM patients after pleural interventions has been disproved in a randomized trial. SUMMARY: Diagnosis of epithelioid MPM can be established on pleural fluid analysis in most patients. The use of BAP1 immunostaining and CDKN2A/p16 fluorescence in-situ hybridization are particularly useful in distinguishing benign from malignant mesothelial proliferations. Clinicians should ensure these investigations are available in the pathological assessment of cases to minimize invasive investigations and the associated risks.
Subject(s)
Lung Neoplasms , Mesothelioma , Pleural Effusion/diagnosis , Pleural Neoplasms , Cyclin-Dependent Kinase Inhibitor p16/analysis , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Mesothelioma/diagnosis , Mesothelioma/pathology , Mesothelioma, Malignant , Pleural Effusion/metabolism , Pleural Neoplasms/diagnosis , Pleural Neoplasms/pathology , Tumor Suppressor Proteins/analysis , Ubiquitin Thiolesterase/analysisABSTRACT
Strategies to prevent mortality from obstetric venous thromboembolism begin with identification, risk stratification and subsequently, implementation of prophylactic measures. We sought to identify the burden of pharmacologic thromboprophylaxis in postpartum women, including the main clinical indications and its uptake in a multireligious population, with Islam as the official religion. A total of 2514 deliveries between 1st January to 31st December 2016, across three centres in Malaysia were reviewed retrospectively from hospital-based registries. 770 (30.62%) patients fulfilled the criteria for thromboprophylaxis based on the revised 2015 criteria proposed by the Royal College of Obstetricians and Gynaecologists. A combination of age, parity, BMI, caesarean section and preterm births were the main indications. One out of the five patients who delivered vaginally required thromboprophylaxis. In our setting with a sizable Muslim population, low molecular weight heparin was the thromboprophylaxis of choice in more than two-third of the patients. The information obtained from this study allows better local resource planning. Impact statement What is already known on this subject: Risk factors for venous thromboembolism in pregnancy and puerperium are largely drawn from registries due to the rarity of the index event. Up to 7% of women require antenatal thromboprophylaxis based on the criteria proposed by the Royal College of Obstetrician and Gynaecologists in 2009. What do the results of this study add: Using the RCOG guideline revised in 2015, a significant proportion of women delivering vaginally would require postnatal thromboprophylaxis based on age, parity and BMI. When either age or parity, both with relatively low odds ratio for thrombosis were omitted, a substantial proportion of women would not achieve the threshold for prophylaxis. Despite a sizable Muslim population in the country, the uptake of low molecular weight heparin was relatively high. What are the implications of these findings for clinical practice and/or future research: Cost-benefit studies should consider the adjusted odds ratio of individual indications on a VTE event. While uptake and acceptability is high, prospective studies on medication adherence is equally pertinent.
Subject(s)
Anticoagulants/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Patient Acceptance of Health Care/statistics & numerical data , Puerperal Disorders/prevention & control , Venous Thromboembolism/prevention & control , Adult , Female , Humans , Islam , Pregnancy , Retrospective Studies , Risk Assessment , Young AdultABSTRACT
BACKGROUND: Antimicrobial dosing in critically ill patients is challenging and model-informed precision dosing (MIPD) software may be used to optimize dosing in these patients. However, few intensive care units (ICU) currently adopt MIPD software use. OBJECTIVES: To determine the usability of MIPD software perceived by ICU clinicians and identify implementation barriers and enablers of software in the ICU. METHODS: Clinicians (pharmacists and medical staff) who participated in a wider multicenter study using MIPD software were invited to participate in this mixed-method study. Participants scored the industry validated Post-study System Usability Questionnaire (PSSUQ, assessing software usability) and Technology Acceptance Model 2 (TAM2, assessing factors impacting software acceptance) survey. Semistructured interviews were used to explore survey responses. The framework approach was used to identify factors influencing software usability and integration into the ICU from the survey and interview data. RESULTS: Seven of the eight eligible clinicians agreed to participate in the study. The PSSUQ usability scores ranked poorer than the reference norms (2.95 vs. 2.62). The TAM2 survey favorably ranked acceptance in all domains, except image. Qualitatively, key enablers to workflow integration included clear and accessible data entry, visual representation of recommendations, involvement of specialist clinicians, and local governance of software use. Barriers included rigid data entry systems and nonconformity of recommendations to local practices. CONCLUSION: Participants scored the MIPD software below the threshold that implies good usability. Factors such as availability of software support by specialist clinicians was important to participants while rigid data entry was found to be a deterrent.
Subject(s)
Intensive Care Units , Software , Humans , Precision Medicine/methods , Surveys and QuestionnairesABSTRACT
OBJECTIVE: Mitofusin-2 (MFN2) is a mitochondrial membrane protein that plays a critical role in regulating mitochondrial fusion and cellular metabolism. To further elucidate the impact of MFN2, this study aimed to investigate its significance on hepatocellular carcinoma (HCC) cell function and its potential role in mediating chemosensitivity. METHODS: This study investigated the effects of silencing and overexpressing MFN2 on the survival, proliferation, invasion and migration abilities, and sorafenib resistance of MHCC97-L HCC cells. Additional experiments were conducted using XAV939 (a ß-catenin inhibitor) and HLY78 (a ß-catenin activator) to further validate these findings. RESULTS: Silencing MFN2 significantly promoted the survival and proliferation of MHCC97-L cells, enhanced their invasion and migration capacities, increased the IC50 of sorafenib, reduced the percentage of TUNEL-positive cells, and decreased the expression of proapoptotic proteins. Additionally, silencing MFN2 markedly induced the nuclear translocation of ß-catenin, increased ß-catenin acetylation levels and enhanced the expression of the downstream regulatory proteins Snail1 and Vimentin while inhibiting E-cadherin expression. Conversely, overexpressing MFN2 reversed the effects observed in MHCC97-L cells mentioned above. The results confirmed that silencing MFN2 activated the ß-catenin/epithelial-mesenchymal transition (EMT) pathway and reduced the sensitivity of cells to sorafenib, which could be reversed by XAV939 treatment. Conversely, overexpression of MFN2 inhibited the ß-catenin/EMT pathway and increased the sensitivity of cells to sorafenib, which could be altered by HLY78. CONCLUSION: Low expression of MFN2 in HCC cells promotes the nuclear translocation of ß-catenin, thereby activating the EMT pathway and mediating resistance to sorafenib.
Subject(s)
Carcinoma, Hepatocellular , Cell Movement , Cell Proliferation , Drug Resistance, Neoplasm , GTP Phosphohydrolases , Liver Neoplasms , Sorafenib , Wnt Signaling Pathway , beta Catenin , Humans , Sorafenib/pharmacology , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/genetics , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , GTP Phosphohydrolases/genetics , GTP Phosphohydrolases/metabolism , Cell Line, Tumor , beta Catenin/metabolism , beta Catenin/genetics , Wnt Signaling Pathway/drug effects , Wnt Signaling Pathway/genetics , Cell Proliferation/drug effects , Cell Movement/drug effects , Cell Movement/genetics , Drug Resistance, Neoplasm/genetics , Drug Resistance, Neoplasm/drug effects , Gene Silencing , Antineoplastic Agents/pharmacology , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Epithelial-Mesenchymal Transition/drug effects , Epithelial-Mesenchymal Transition/genetics , Apoptosis/drug effects , Apoptosis/genetics , Gene Expression Regulation, Neoplastic/drug effectsABSTRACT
INTRODUCTION: Critically ill patients are at risk of suboptimal beta-lactam antibiotic (beta-lactam) exposure due to the impact of altered physiology on pharmacokinetics. Suboptimal concentrations can lead to treatment failure or toxicity. Therapeutic drug monitoring (TDM) involves adjusting doses based on measured plasma concentrations and individualising dosing to improve the likelihood of improving exposure. Despite its potential benefits, its adoption has been slow, and data on implementation, dose adaptation and safety are sparse. The aim of this trial is to assess the feasibility and fidelity of implementing beta-lactam TDM-guided dosing in the intensive care unit setting. METHODS AND ANALYSIS: A beta-lactam antibiotic Dose AdaPtation feasibility randomised controlled Trial using Therapeutic Drug Monitoring (ADAPT-TDM) is a single-centre, unblinded, feasibility randomised controlled trial aiming to enroll up to 60 critically ill adult participants (≥18 years). TDM and dose adjustment will be performed daily in the intervention group; the standard of care group will undergo plasma sampling, but no dose adjustment. The main outcomes include: (1) feasibility of recruitment, defined as the number of participants who are recruited from a pool of eligible participants, and (2) fidelity of TDM, defined as the degree to which TDM as a test is delivered as intended, from accurate sample collection, sample processing to result availability. Secondary outcomes include target attainment, uptake of TDM-guided dosing and incidence of neurotoxicity, hepatotoxicity and nephrotoxicity. ETHICS AND DISSEMINATION: This study has been approved by the Alfred Hospital human research ethics committee, Office of Ethics and Research Governance (reference: Project No. 565/22; date of approval: 22/11/2022). Prospective consent will be obtained and the study will be conducted in accordance with the Declaration of Helsinki. The finalised manuscript, including aggregate data, will be submitted for publication in a peer reviewed journal. ADAPT-TDM will determine whether beta-lactam TDM-guided dose adaptation is reproducible and feasible and provide important information required to implement this intervention in a phase III trial. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry, ACTRN12623000032651.
Subject(s)
Anti-Bacterial Agents , Critical Illness , Drug Monitoring , Feasibility Studies , beta-Lactams , Humans , Drug Monitoring/methods , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Critical Illness/therapy , beta-Lactams/administration & dosage , beta-Lactams/pharmacokinetics , Randomized Controlled Trials as Topic , Intensive Care UnitsABSTRACT
PURPOSE: Early recognition and effective treatment of sepsis improves outcomes in critically ill patients. However, antibiotic exposures are frequently suboptimal in the intensive care unit (ICU) setting. We describe the feasibility of the Bayesian dosing software Individually Designed Optimum Dosing Strategies (ID-ODS™), to reduce time to effective antibiotic exposure in children and adults with sepsis in ICU. METHODS: A multi-centre prospective, non-randomised interventional trial in three adult ICUs and one paediatric ICU. In a pre-intervention Phase 1, we measured the time to target antibiotic exposure in participants. In Phase 2, antibiotic dosing recommendations were made using ID-ODS™, and time to target antibiotic concentrations were compared to patients in Phase 1 (a pre-post-design). RESULTS: 175 antibiotic courses (Phase 1 = 123, Phase 2 = 52) were analysed from 156 participants. Across all patients, there was no difference in the time to achieve target exposures (8.7 h vs 14.3 h in Phase 1 and Phase 2, respectively, p = 0.45). Sixty-one courses in 54 participants failed to achieve target exposures within 24 h of antibiotic commencement (n = 36 in Phase 1, n = 18 in Phase 2). In these participants, ID-ODS™ was associated with a reduction in time to target antibiotic exposure (96 vs 36.4 h in Phase 1 and Phase 2, respectively, p < 0.01). These patients were less likely to exhibit subtherapeutic antibiotic exposures at 96 h (hazard ratio (HR) 0.02, 95% confidence interval (CI) 0.01-0.05, p < 0.01). There was no difference observed in in-hospital mortality. CONCLUSIONS: Dosing software may reduce the time to achieve target antibiotic exposures. It should be evaluated further in trials to establish its impact on clinical outcomes.
Subject(s)
Anti-Bacterial Agents , Sepsis , Adult , Child , Humans , Anti-Bacterial Agents/therapeutic use , Bayes Theorem , Critical Illness/therapy , Intensive Care Units, Pediatric , Prospective Studies , Sepsis/drug therapy , SoftwareABSTRACT
Commercially available carbon nanotubes and nanofibers were analyzed to examine possible relationships between their Brunauer-Emmett-Teller specific surface areas (SSAs) and their physical and chemical properties. Properties found to influence surface area were number of walls/diameter, impurities, and surface functionalization with hydroxyl and carboxyl groups. Characterization by electron microscopy, energy-dispersive X-ray spectrometry, thermogravimetric analysis, and elemental analysis indicates that SSA can provide insight on carbon nanomaterials properties, which can differ vastly depending on synthesis parameters and post-production treatments. In this study, how different properties may influence surface area is discussed. The materials examined have a wide range of surface areas. The measured surface areas differed from product specifications, to varying degrees, and between similar products. Findings emphasize the multiple factors that influence surface area and mark its utility in carbon nanomaterial characterization, a prerequisite to understanding their potential applications and toxicities. Implications for occupational monitoring are discussed.
Subject(s)
Industry , Nanofibers/analysis , Nanotubes, Carbon/analysis , Microscopy, Electron, Transmission , Nanofibers/chemistry , Nanotechnology/methods , Nanotubes, Carbon/chemistry , Spectrophotometry, Atomic , Surface Properties , ThermogravimetryABSTRACT
Beta-lactams are an important family of antibiotics used to treat infections and are commonly used in critically ill patients. Optimal use of these drugs in the intensive care unit (ICU) is important because of the serious complications from sepsis. Target beta-lactam antibiotic exposures may be chosen using fundamental principles of beta-lactam activity derived from pre-clinical and clinical studies, although the debate regarding optimal beta-lactam exposure targets is ongoing. Attainment of target exposures in the ICU requires overcoming significant pharmacokinetic (PK) and pharmacodynamic (PD) challenges. For beta-lactam drugs, the use of therapeutic drug monitoring (TDM) to confirm if the desired exposure targets are achieved has shown promise, but further data are required to determine if improvement in infection-related outcomes can be achieved. Additionally, beta-lactam TDM may be useful where a relationship exists between supratherapeutic antibiotic exposure and drug adverse effects. An ideal beta-lactam TDM service should endeavor to efficiently sample and report results in identified at-risk patients in a timely manner. Consensus beta-lactam PK/PD targets associated with optimal patient outcomes are lacking and should be a focus for future research.
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INTRODUCTION: Broad-spectrum antibiotics such as beta-lactams and vancomycin are frequently used to treat critically ill patients, however, a significant number do not achieve target exposures. Therapeutic drug monitoring (TDM) combined with Bayesian forecasting dosing software may improve target attainment in these patients. This study aims to describe the efficiency of dosing software for achieving target exposures of selected beta-lactam antibiotics and vancomycin in critically ill patients. METHODS: A prospective cohort study was undertaken in an adult intensive care unit (ICU). Patients prescribed vancomycin, piperacillin-tazobactam and meropenem were included if they exhibited a subtherapeutic or supratherapeutic exposure informed by TDM. The dosing software, ID-ODS™, was used to generate dosing recommendations which could be either accepted or rejected by the treating team. Repeat antibiotic TDM were requested to determine if target exposures were achieved. RESULTS: Between March 2020 and December 2021, 70 were included in the analysis. Software recommendations were accepted for 56 patients (80%) with 50 having repeated antibiotic measurements. Forty-three of the 50 patients (86%) achieved target exposures after one software recommendation, with 3 of the remaining 7 patients achieving target exposures after 2. Forty-seven patients out of the 50 patients (94%) achieved the secondary outcome of clinical cure. There were no antibiotic exposure-related adverse events reported. CONCLUSION: The use of TDM combined with Bayesian forecasting dosing software increases the efficiency for achieving target antibiotic exposures in the ICU. Clinical trials comparing this approach with other dosing strategies are required to further validate these findings.
Subject(s)
Anti-Bacterial Agents , Vancomycin , Adult , Humans , Anti-Bacterial Agents/therapeutic use , Prospective Studies , Critical Illness/therapy , Bayes Theorem , beta-Lactams/therapeutic use , SoftwareABSTRACT
BACKGROUND: Chinese bayberry (Myrica rubra Sieb. and Zucc.) is a subtropical evergreen tree originating in China. It has been cultivated in southern China for several thousand years, and annual production has reached 1.1 million tons. The taste and high level of health promoting characters identified in the fruit in recent years has stimulated its extension in China and introduction to Australia. A limited number of co-dominant markers have been developed and applied in genetic diversity and identity studies. Here we report, for the first time, a survey of whole genome shotgun data to develop a large number of simple sequence repeat (SSR) markers to analyse the genetic diversity of the common cultivated Chinese bayberry and the relationship with three other Myrica species. RESULTS: The whole genome shotgun survey of Chinese bayberry produced 9.01Gb of sequence data, about 26x coverage of the estimated genome size of 323 Mb. The genome sequences were highly heterozygous, but with little duplication. From the initial assembled scaffold covering 255 Mb sequence data, 28,602 SSRs (≥5 repeats) were identified. Dinucleotide was the most common repeat motif with a frequency of 84.73%, followed by 13.78% trinucleotide, 1.34% tetranucleotide, 0.12% pentanucleotide and 0.04% hexanucleotide. From 600 primer pairs, 186 polymorphic SSRs were developed. Of these, 158 were used to screen 29 Chinese bayberry accessions and three other Myrica species: 91.14%, 89.87% and 46.84% SSRs could be used in Myrica adenophora, Myrica nana and Myrica cerifera, respectively. The UPGMA dendrogram tree showed that cultivated Myrica rubra is closely related to Myrica adenophora and Myrica nana, originating in southwest China, and very distantly related to Myrica cerifera, originating in America. These markers can be used in the construction of a linkage map and for genetic diversity studies in Myrica species. CONCLUSION: Myrica rubra has a small genome of about 323 Mb with a high level of heterozygosity. A large number of SSRs were identified, and 158 polymorphic SSR markers developed, 91% of which can be transferred to other Myrica species.
Subject(s)
Genome, Plant , Microsatellite Repeats , Myrica/genetics , Base Sequence , China , Cluster Analysis , Evolution, Molecular , Expressed Sequence Tags , Polymorphism, GeneticABSTRACT
Carbonaceous aerosols play an important role in climate, visibility, air quality, and human health effects, and they have been routinely monitored in workplace and environmental settings. Different thermal analysis methods have been applied to determine the carbon content of carbonaceous aerosols. Good agreement between results for total carbon (TC) generally has been found, but the organic and elemental carbon (OC and EC) fractions determined by different methods often disagree. Measurement uncertainty is mainly due to pyrolysis and charring of OC sample components. Lack of reference materials has impeded progress on method standardization and understanding method biases. A relatively simple method for generating matched filter sets having known OC-EC contents is reported. After generation and analysis of each set to confirm agreement between filters, the filter sets were distributed to six laboratories for an interlaboratory comparison. Analytical results indicate a uniform carbon distribution for the filter sets and good agreement between the participating laboratories. Relative standard deviations (RSDs) for mean TC (OC + EC), OC, and EC results for seven laboratories were <10, 11, and 12% (respectively). Except for one EC result (RSD = 16%), RSDs reported by individual laboratories for TC, OC, and EC were <12%. The method of filter generation is generally applicable and reproducible. Depending on the application, different filter loadings and types of OC materials can be employed. Matched filter sets prepared by the described approach can be used for determining the accuracy of OC-EC methods and thereby contribute to method standardization.
Subject(s)
Carbon/analysis , Environmental Monitoring/methods , Filtration/instrumentation , Aerosols/analysis , Air Filters , Air Pollutants/analysis , Carbon/classification , Humans , Particle Size , Particulate MatterABSTRACT
BACKGROUND: Precision dosing programs are promising tools for optimising antimicrobial dosing. Selecting the ideal program for local application may be challenging due to the large variety of available programs with differing characteristics. OBJECTIVES: The objectives of this study were to systematically identify available precision dosing software programs to optimize antimicrobial dosing and describe the characteristics of each program. Details on the ability of programs to provide beta-lactam dosing support was also gathered. SOURCES: A systematic review search strategy was used to identify candidate software programs described in the literature in Embase and PubMed. A detailed survey was then developed to identify characteristics of programs, including details on the underlying methodology driving dosing software recommendations, interface characteristics, costs and regulatory affairs. Software developers from all identified programs were invited to participate in the survey. CONTENT: The systematic search results identified 18 programs. Fifteen developers responded to the survey (83%) and 11 programs provide dosing support for at least one beta-lactam. Fourteen programs can utilize measured drug concentrations to generate dosing recommendations, with 13 able to generate empiric dosing recommendations. Six programs integrate with local electronic health records and four are registered with at least one regulatory agency. Pharmacokinetic models in combination with Bayesian statistics is the most common methodology used to generate dosing recommendations, with 14 programs utilizing this method. IMPLICATIONS: There was significant variability in the available antimicrobial profiles and characteristics among dosing software programs. As healthcare providers will differ in their requirements within their local settings, clinicians should use these findings to identify potential candidate programs and, if feasible, trial these to ensure they meet their specific requirements.
Subject(s)
Anti-Bacterial Agents , Anti-Infective Agents , Bayes Theorem , Follow-Up Studies , Humans , Software , beta-LactamsABSTRACT
Antimicrobial dosing in the intensive care unit (ICU) can be problematic due to various challenges including unique physiological changes observed in critically ill patients and the presence of pathogens with reduced susceptibility. These challenges result in reduced likelihood of standard antimicrobial dosing regimens achieving target exposures associated with optimal patient outcomes. Therefore, the aim of this review is to explore the various methods for optimisation of antimicrobial dosing in ICU patients. Dosing nomograms developed from pharmacokinetic/statistical models and therapeutic drug monitoring are commonly used. However, recent advances in mathematical and statistical modelling have resulted in the development of novel dosing software that utilise Bayesian forecasting and/or artificial intelligence. These programs utilise therapeutic drug monitoring results to further personalise antimicrobial therapy based on each patient's clinical characteristics. Studies quantifying the clinical and cost benefits associated with dosing software are required before widespread use as a point-of-care system can be justified.
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BACKGROUND & AIM: Active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR), which applies to cardiac arrests with contraindication of standard chest compressions (SCC) CPR, has been utilized in cardiac arrest. However, the efficacy and safety of AACD-CPR still remained controversy. This analysis was designed to comprehensively compare AACD versus SCC-CPR in patients with cardiac arrest. METHODS: We searched the Cochrane Library, PubMed, EMBASE, Web of Science and CNKI up to April 22, 2019. Mean difference (MD) and risk ratio (RR) with its 95% confidence intervals (CIs) were estimated to compare outcomes of the groups. Our primary outcomes were restoration of spontaneous circulation (ROSC) and short-term survival. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2 and Stata 12.0. RESULTS: A total of seventeen studies (Nâ¯=â¯1647 patients) were identified for the present analysis. Compared with standard CPR, AACD-CPR was superior in restoration of spontaneous circulation (ROSC) and short-term survival, with pooled RRs of 1.38 (95% CI 1.23-1.55; Pâ¯<â¯0.00001) and RRs of 2.05 (95% CI 1.69-2.50; Pâ¯<â¯0.00001) respectively. In addition, significant superiority of AACD-CPR was found in incidence of fracture, long-term survival, pressure of end-tidal carbon dioxide (PETCO2), coronary perfusion pressure (CPP) and adverse events. No significant difference was observed in incidence of vomiting. CONCLUSIONS: Generally, in this combined analysis we found a statistically significant improvement in survival and ROSC with the use of AACD-CPR as compared with the use of standard CPR. There was also significant improvement in incidence of fracture, long-term survival, PETCO2 and CPP with AACD-CPR in comparison with standard CPR; results were not statistically different between the groups regarding to vomiting rate and adverse events. The standardized, diversified and individualized methods of clinical operation of AACD-CPR need exploration and expectingly serve as a guideline for clinical application of AACD-CPR in the future.
Subject(s)
Cardiopulmonary Resuscitation/adverse effects , Cardiopulmonary Resuscitation/methods , Heart Arrest/therapy , Resuscitation/adverse effects , Resuscitation/methods , Abdomen , Aged , Contraindications , Female , Humans , Lower Body Negative Pressure/adverse effects , Lower Body Negative Pressure/methods , Male , Middle Aged , Odds Ratio , Pressure , Randomized Controlled Trials as Topic , Thorax , Treatment OutcomeABSTRACT
A 75-year-old retired teacher presents with dysphagia and weight loss for a duration of 6 months. Her gastroscopy showed two synchronous submucosal masses. A 7 cm polypoid mass was seen at the distal oesophagus, arising from a thick stalk and a 4 cm mass seen at the cardia. The biopsies showed high-grade sarcomatoid cancer. Staging CT scan and Positron Emission Tomography scan did not show any distant metastasis except a lesion in the rectum that was subsequently found to be tubulovillous adenoma on transanal excision. The patient was managed with Ivor Lewis oesophagectomy. The biopsies of resection specimen showed spindle cell/sarcomatoid carcinoma with a component of poorly differentiated neuroendocrine carcinoma in oesophageal tumour and a small component of conventional invasive squamous cell carcinoma in tumour at cardia. The patient recovered well after surgery. Since then, she has completed adjuvant chemoradiotherapy. No recurrence has been noted in 10 months follow-up.